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1

Bovenkamp, Daniela, Alexander Micko, Jeremias Püls, Fabian Placzek, Romana Höftberger, Greisa Vila, Rainer Leitgeb, et al. "Line Scan Raman Microspectroscopy for Label-Free Diagnosis of Human Pituitary Biopsies." Molecules 24, no. 19 (October 4, 2019): 3577. http://dx.doi.org/10.3390/molecules24193577.

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Pituitary adenomas are neoplasia of the anterior pituitary gland and can be subdivided into hormone-producing tumors (lactotroph, corticotroph, gonadotroph, somatotroph, thyreotroph or plurihormonal) and hormone-inactive tumors (silent or null cell adenomas) based on their hormonal status. We therefore developed a line scan Raman microspectroscopy (LSRM) system to detect, discriminate and hyperspectrally visualize pituitary gland from pituitary adenomas based on molecular differences. By applying principal component analysis followed by a k-nearest neighbor algorithm, specific hormone states were identified and a clear discrimination between pituitary gland and various adenoma subtypes was achieved. The classifier yielded an accuracy of 95% for gland tissue and 84–99% for adenoma subtypes. With an overall accuracy of 92%, our LSRM system has proven its potential to differentiate pituitary gland from pituitary adenomas. LSRM images based on the presence of specific Raman bands were created, and such images provided additional insight into the spatial distribution of particular molecular compounds. Pathological states could be molecularly differentiated and characterized with texture analysis evaluating Grey Level Cooccurrence Matrices for each LSRM image, as well as correlation coefficients between LSRM images.
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2

Segarra, Ana B., Isabel Prieto, Inmaculada Banegas, Magdalena Martínez-Cañamero, Ana B. Villarejo, Germán Domínguez-Vías, Marc de Gasparo, and Manuel Ramírez-Sánchez. "Interaction between Angiotensinase Activities in Pituitary and Adrenal Glands of Wistar–Kyoto and Spontaneously Hypertensive Rats under Hypotensive or Hypertensive Treatments." International Journal of Molecular Sciences 22, no. 15 (July 22, 2021): 7823. http://dx.doi.org/10.3390/ijms22157823.

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In the present study, we analyzed the activity of several aminopeptidases (angiotensinases) involved in the metabolism of various angiotensin peptides, in pituitary and adrenal glands of untreated Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHR) or treated with the antihypertensive drugs captopril and propranolol or with the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME). Intra- and inter-gland correlations between angiotensinase activities were also calculated. Membrane-bound alanyl-, cystinyl-, and glutamyl-aminopeptidase activities were determined fluorometrically using aminoacyl-β-naphthylamide as substrates. Depending on the type of angiotensinase analyzed, the results reflect a complex picture showing substantial differences between glands, strains, and treatments. Alanyl-aminopeptidase responsible for the metabolism of Ang III to Ang IV appears to be the most active angiotensinase in both pituitary and adrenals of WKY and particularly in SHR. Independently of treatment, most positive correlations are observed in the pituitary gland of WKY whereas such positive correlations are predominant in adrenals of SHR. Negative inter-gland correlations were observed in control SHR and L-NAME treated WKY. Positive inter-gland correlations were observed in captopril-treated SHR and propranolol-treated WKY. These results may reflect additional mechanisms for increasing or decreasing systolic blood pressure in WKY or SHR.
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3

Ottenhausen, Malte, Imithri Bodhinayake, Matei A. Banu, Philip E. Stieg, and Theodore H. Schwartz. "Vincent du Vigneaud: following the sulfur trail to the discovery of the hormones of the posterior pituitary gland at Cornell Medical College." Journal of Neurosurgery 124, no. 5 (May 2016): 1538–42. http://dx.doi.org/10.3171/2015.5.jns141952.

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In 1955, Vincent du Vigneaud (1901–1978), the chairman of the Department of Biochemistry at Cornell University Medical College, was awarded the Nobel Prize for Chemistry for his research on insulin and for the first synthesis of the posterior pituitary hormones—oxytocin and vasopressin. His tremendous contribution to organic chemistry, which began as an interest in sulfur-containing compounds, paved the way for a better understanding of the pituitary gland and for the development of diagnostic and therapeutic tools for diseases of the pituitary. His seminal research continues to impact neurologists, endocrinologists, and neurosurgeons, and enables them to treat patients who had no alternatives prior to du Vigneaud’s breakthroughs in peptide structure and synthesis. The ability of neurosurgeons to aggressively operate on parasellar pathology was directly impacted and related to the ability to replace these hormones after surgery. The authors review the life and career of Vincent du Vigneaud, his groundbreaking discoveries, and his legacy of the understanding and treatment of the pituitary gland in health and disease.
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4

Gounden, Verena, Yashna D. Rampursat, and Ishwarlal Jialal. "Secretory tumors of the pituitary gland: a clinical biochemistry perspective." Clinical Chemistry and Laboratory Medicine (CCLM) 57, no. 2 (December 19, 2018): 150–64. http://dx.doi.org/10.1515/cclm-2018-0552.

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Abstract The pituitary gland is responsible for the production and/or secretion of various hormones that play a vital role in regulating endocrine function within the body. Secretory tumors of the anterior pituitary predominantly, pituitary adenomas, collectively account for 10%–25% of central nervous system tumors requiring surgical treatment. The most common secretory tumors are prolactinomas, which can be diagnosed by basal prolactin levels. Acromegaly can be diagnosed by basal insulin growth-like factor 1 levels and the failure of growth hormone (GH) to suppress during an oral glucose tolerance test. Cushing disease can be diagnosed by demonstrating hypercortisolemia evidenced by increased salivary cortisol levels in the evening, increased urine free cortisol excretion and failure of plasma cortisol to suppress following oral dexamethasone given overnight (1.0 mg). We also discuss the diagnosis of the rarer thyroid-stimulating hormone and gonadotrophin secretory tumors. Morbidity is associated with tumor occurrence, clinical sequelae as well as the related medical, surgical and radiological management. This review focuses on the pathogenesis of secretory tumors of the anterior pituitary with emphasis on molecular mechanisms associated with tumorigenesis and the major role of the clinical chemistry laboratory in diagnosis and management of these tumors.
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5

Mikołajczyk, Anita, and Dagmara Złotkowska. "Subclinical Lipopolysaccharide from Salmonella Enteritidis Induces Dysregulation of Bioactive Substances from Selected Brain Sections and Glands of Neuroendocrine Axes." Toxins 11, no. 2 (February 2, 2019): 91. http://dx.doi.org/10.3390/toxins11020091.

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Bacterial lipopolysaccharide (LPS) can contribute to the pathogenesis and the clinical symptoms of many diseases such as cancer, mental disorders, neurodegenerative as well as metabolic diseases. The asymptomatic carrier state of Salmonella spp. is a very important public health problem. A subclinical single dose of LPS obtained from S. Enteritidis (5 μg/kg, i.v.) was administered to discern the consequences of changes of various brain peptides such as corticotropin-releasing hormone (CRH), gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), galanin (GAL), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP), and vasoactive intestinal polypeptide (VIP) in selected clinically important brain sections and endocrine glands of the hypothalamic-pituitary-adrenal (HPA), -thyroid (HPT), -ovarian (HPO) axes. The study was conducted on ten immature crossbred female pigs. The brain peptides were extracted from the hypothalamus (medial basal hypothalamus, preoptic area, lateral hypothalamic area, mammillary bodies, and the stalk median eminence), and pituitary gland (adenohypophysis and neurohypophysis) sections and from the ovaries and adrenal and thyroid glands. There was no difference in health status between LPS and the control groups during the period of the experiment. Nevertheless, even a low single dose of LPS from S. Enteritidis that did not result in any clinical symptoms of disease induced dysregulation of various brain peptides, such as CRH, GnRH, TRH, GAL, NPY, SOM, SP, and VIP in selected brain sections of hypothalamus, pituitary gland and in the endocrine glands of the HPA, HPO, and HPT axes. In conclusion, the obtained results clearly show that subclinical LPS from S. Enteritidis can affect the brain chemistry structure and dysregulate bioactive substance from selected brain sections and glands of the neuroendocrine axes. The exact mechanisms by which LPS can influence major neuroendocrine axes are not fully understood and require further studies.
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6

Risi, Renata, Simonetta Masieri, Eleonora Poggiogalle, Mikiko Watanabe, Alessandra Caputi, Rossella Tozzi, Elena Gangitano, et al. "Nickel Sensitivity Is Associated with GH-IGF1 Axis Impairment and Pituitary Abnormalities on MRI in Overweight and Obese Subjects." International Journal of Molecular Sciences 21, no. 24 (December 20, 2020): 9733. http://dx.doi.org/10.3390/ijms21249733.

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Nickel (Ni) is a ubiquitous metal, the exposure of which is implied in the development of contact dermatitis (nickel allergic contact dermatitis (Ni-ACD)) and Systemic Ni Allergy Syndrome (SNAS), very common among overweight/obese patients. Preclinical studies have linked Ni exposure to abnormal production/release of Growth Hormone (GH), and we previously found an association between Ni-ACD/SNAS and GH-Insulin-like growth factor 1 (IGF1) axis dysregulation in obese individuals, altogether suggesting a role for this metal as a pituitary disruptor. We herein aimed to directly evaluate the pituitary gland in overweight/obese patients with signs/symptoms suggestive of Ni allergy, exploring the link with GH secretion; 859 subjects with overweight/obesity and suspected of Ni allergy underwent Ni patch tests. Among these, 106 were also suspected of GH deficiency (GHD) and underwent dynamic testing as well as magnetic resonance imaging for routine follow up of benign diseases or following GHD diagnosis. We report that subjects with Ni allergies show a greater GH-IGF1 axis impairment, a higher prevalence of Empty Sella (ES), a reduced pituitary volume and a higher normalized T2 pituitary intensity compared to nonallergic ones. We hypothesize that Ni may be detrimental to the pituitary gland, through increased inflammation, thus contributing to GH-IGF1 axis dysregulation.
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7

DeAtley, Kasey L., Michelle L. Colgrave, Angela Cánovas, Gene Wijffels, Ryan L. Ashley, Gail A. Silver, Gonzalo Rincon, et al. "Neuropeptidome of the Hypothalamus and Pituitary Gland of Indicine × Taurine Heifers: Evidence of Differential Neuropeptide Processing in the Pituitary Gland before and after Puberty." Journal of Proteome Research 17, no. 5 (March 7, 2018): 1852–65. http://dx.doi.org/10.1021/acs.jproteome.7b00875.

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8

Penta, Laura, Carla Bizzarri, Michela Panichi, Antonio Novelli, Francesca Romana Lepri, Marco Cappa, and Susanna Esposito. "Identification of a Novel PROP1 Mutation in a Patient with Combined Pituitary Hormone Deficiency and Enlarged Pituitary." International Journal of Molecular Sciences 20, no. 8 (April 16, 2019): 1875. http://dx.doi.org/10.3390/ijms20081875.

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Growth hormone deficiency (GHD) can be present from the neonatal period to adulthood and can be the result of congenital or acquired insults. In addition, GHD can be classified into two types: isolated growth hormone deficiency (IGHD) and combined pituitary hormone deficiency (CPHD). CPHD is a disorder characterized by impaired production of two or more anterior and/or posterior pituitary hormones. Many genes implicated in CPHD remain to be identified. Better genetic characterization will provide more information about the disorder and result in important genetic counselling because a number of patients with hypopituitarism represent familial cases. To date, PROP1 mutations represent the most common known genetic cause of CPHD both in sporadic and familial cases. We report a novel mutation in the PROP1 gene in an infant with CPHD and an enlarged pituitary gland. Close long-term follow-up will reveal other possible hormonal defects and pituitary involution.
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9

Liu, Qian, Taoyang Yuan, Hua Gao, Songbai Gui, Yazhuo Zhang, and Chuzhong Li. "Anti-EGFL7 antibodies inhibit rat prolactinoma MMQ cells proliferation and PRL secretion." Open Chemistry 16, no. 1 (July 9, 2018): 621–26. http://dx.doi.org/10.1515/chem-2018-0064.

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AbstractProlactinoma is the most frequently diagnosed pituitary tumors. Dopamine agonists (DAs) are recognized as first-line therapy; however, approximately 10% patients will develop resistance to DAs therapy. Consequently, a large number of investigations have been carried out to identify novel therapeutic targets. Recently, studies have suggested that epidermal growth factor-like domain 7 (EGFL7) can promote tumor growth, invasion, and angiogenesis. We previously reported that overexpression of EGFL7 might play a crucial role in hormone-producing pituitary adenomas. In the present study, we now demonstrated a significantly higher protein expression of EGFL7 in prolactinoma compared with the normal pituitary gland. However, inhibition of EGFL7 with anti-EGFL7 antibodies significantly reduced the proliferation and PRL secretion of rat prolactinoma MMQ cells. Notably, in vitro administration of anti-EGFL7 antibodies significantly induced MMQ cells apoptosis in a dose-dependent manner. In conclusion, our finding suggests that EGFL7 is significantly overexpressed in prolactinoma and inhibition of EGFL7 with antibodies promoted MMQ cells apoptosis and inhibited PRL secretion. Thus, EGFL7 may serve as a potential novel therapeutic target for prolactinomas.
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10

Kiełbasa, Anna, Renata Gadzała-Kopciuch, and Bogusław Buszewski. "Cytokines-Biogenesis and Their Role in Human Breast Milk and Determination." International Journal of Molecular Sciences 22, no. 12 (June 9, 2021): 6238. http://dx.doi.org/10.3390/ijms22126238.

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Cytokines play a huge role in many biological processes. Their production, release and interactions are subject to a very complex mechanism. Cytokines are produced by all types of cells, they function very differently and they are characterized by synergism in action, antagonism, and aggregation activity, opposing action of one cytokine, overlapping activity, induction of another cytokine, inhibition of cytokine synthesis at the mRNA level as well as autoregulation-stimulation or inhibition of own production. The predominance of pro-inflammatory cytokines leads to a systemic inflammatory response, and anti-inflammatory-to an anti-inflammatory response. They regulate the organism’s immune response and protect it against sudden disturbances in homeostasis. The synthesis and activity of cytokines are influenced by the central nervous system through the endocrine system (pituitary gland, adrenal glands).
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11

Hymer, W. C., R. E. Grindeland, T. Salada, P. Nye, E. J. Grossman, and P. K. Lane. "Experimental modification of rat pituitary growth hormone cell function during and after spaceflight." Journal of Applied Physiology 80, no. 3 (March 1, 1996): 955–70. http://dx.doi.org/10.1152/jappl.1996.80.3.955.

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Space-flown rats show a number of flight-induced changes in the structure and function of pituitary growth hormone (GH) cells after in vitro postflight testing (W. C. Hymen, R. E. Grindeland, I. Krasnov, I, Victorov, K. Motter, P. Mukherjee, K. Shellenberger, and M. Vasques. J. Appl. Physiol. 73, Suppl.: 151S-157S, 1992). To evaluate the possible effects of microgravity on growth hormone (GH) cells themselves, freshly dispersed rat anterior pituitary gland cells were seeded into vials containing serum +/- microM hydrocortisone (HC) before flight. Five different cell preparations were used: the entire mixed-cell population of various hormone-producing cell types, cells of density < 1.071 g/cm3 (band 1), cells of density > 1.071 g/cm3 (band 2), and cells prepared from either the dorsal or ventral part of the gland. Relative to ground control samples, bioactive GH released from dense cells during flight was reduced in HC-free medium but was increased in HC-containing medium. Band 1 and mixed cells usually showed opposite HC-dependent responses. Release of bioactive GH from ventral flight cells was lower; postflight responses to GH-releasing hormone challenge were reduced, and the cytoplasmic area occupied by GH in the dense cells was greater. Collectively, the data show that the chemistry and cellular makeup of the culture system modifies the response of GH cells to microgravity. As such, these cells offer a system to identify gravisensing mechanisms in secretory cells in future microgravity research.
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12

Etoh, Sachise, Kenji Hamase, Akiko Morikawa, Tomohiro Ohgusu, and Kiyoshi Zaitsu. "Enantioselective visualization of D-alanine in rat anterior pituitary gland: localization to ACTH-secreting cells." Analytical and Bioanalytical Chemistry 393, no. 1 (October 4, 2008): 217–23. http://dx.doi.org/10.1007/s00216-008-2401-5.

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13

Speziali, M., and E. Sabbioni. "Minor and trace element contents in pituitary gland of “normal” humans: an evaluation of analytical data." Microchemical Journal 79, no. 1-2 (January 2005): 383–91. http://dx.doi.org/10.1016/j.microc.2004.08.010.

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14

XIONG, Xingui, Qinghua LIANG, Jiang CHEN, Rong FAN, and Tianli CHENG. "Proteomics Profiling of Pituitary, Adrenal Gland, and Splenic Lymphocytes in Rats with Middle Cerebral Artery Occlusion." Bioscience, Biotechnology, and Biochemistry 73, no. 3 (March 23, 2009): 657–64. http://dx.doi.org/10.1271/bbb.80717.

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15

Tury, A., G. Mairet-Coello, F. Poncet, C. Jacquemard, P. Y. Risold, D. Fellmann, and B. Griffond. "QSOX sulfhydryl oxidase in rat adenohypophysis: localization and regulation by estrogens." Journal of Endocrinology 183, no. 2 (November 2004): 353–63. http://dx.doi.org/10.1677/joe.1.05842.

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The expression of the rat quiescin sulfhydryl oxidase (rQSOX) and its putative regulation by estrogens were investigated in the adenohypophysis. Immunohistochemical observations revealed that rQSOX protein is abundantly expressed throughout the anterior lobe of the pituitary, and can be found in almost all the different cell populations. However, as shown by double immunohisto-chemistry, the cells displaying the strongest rQSOX labeling belong to a subset of gonadotrophs. Immunoelectron microscopy showed that, in adenohypophyseal cells, the protein is linked to the membranes of the rough endoplasmic reticulum, the Golgi apparatus and to dense-core secretory granules. These results are consistent with the secretion of the protein and its presumed role in the extracellular matrix. According to its sulfhydryl oxidase function, rQSOX could also participate in the intracellular folding of secreted proteins or hormones like LH and FSH and act as an endogenous redox modulator of hormonal secretion. A semiquantitative RT-PCR analysis of rQSOX level across the estrous cycle and the fact that chronic administration of 17 β-estradiol to ovariectomized rats led to a sustained up-regulation of rQSOX in the pituitary suggest that rQSOX expression is controlled by sex hormone levels. Further investigations are needed in order to elucidate its precise roles in that gland and the mechanisms of its regulation.
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16

Lan, Xiaolei, Qian Liu, Hua Gao, Zhenye Li, and Yazhuo Zhang. "Anti-c-myc efficacy block EGFL7 induced prolactinoma tumorigenesis." Open Chemistry 17, no. 1 (December 31, 2019): 1501–8. http://dx.doi.org/10.1515/chem-2019-0151.

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AbstractResistance to Dopamine agonists therapy is still a key factor that hinders the clinical treatment of prolactinoma. Consequently, a large number of investigations have been carried out to identify novel therapeutic targets. Our previous studies have suggested that the epidermal growth factor-like domain 7 (EGFL7) plays a crucial role in tumorigenesis of pituitary adenomas via EGFR/AKT/MAPK signaling pathway. In the present research, we found a positive staining of c-myc intimately associated with high-level EGFL7 in invasive prolactinoma compared to non-invasive prolactinoma and the normal pituitary gland. Meanwhile, PI3K/Akt and MAPK signaling cascades closely related to the activation of c-myc. Therefore, this research was conducted to explore the cooperation effect of c-myc and EGFL7 in prolactinoma. The inhibition of c-myc with anti-c-myc antibodies significantly reduced the proliferation, PRL secretion and invasion of rat prolactinoma MMQ cells. Notably, down regulation c-Myc by in vitro administration of anti-c-Myc antibodies could significantly depress EGFL7 induced MMQ cell proliferation, PRL secretion and invasion. An anti-c-Myc antibody could block EGFL7 induced Akt activation, but the expression of p-ERK was not altered by an anti-c-Myc antibody. Thus, our results suggest that anti-c-myc efficacy could block EGFL7 induced prolactinoma tumorigenesis via inhibited Akt activation in MMQ cells.
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17

Cumberland, Angela L., Jonathan J. Hirst, Emilio Badoer, Stefan A. Wudy, Ronda F. Greaves, Margaret Zacharin, and David W. Walker. "The Enigma of the Adrenarche: Identifying the Early Life Mechanisms and Possible Role in Postnatal Brain Development." International Journal of Molecular Sciences 22, no. 9 (April 21, 2021): 4296. http://dx.doi.org/10.3390/ijms22094296.

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Dehydroepiandrosterone (DHEA) and its sulfated metabolite (DHEAS) are dynamically regulated before birth and the onset of puberty. Yet, the origins and purpose of increasing DHEA[S] in postnatal development remain elusive. Here, we draw attention to this pre-pubertal surge from the adrenal gland—the adrenarche—and discuss whether this is the result of intra-adrenal gene expression specifically affecting the zona reticularis (ZR), if the ZR is influenced by the hypothalamic-pituitary axis, and the possible role of spino-sympathetic innervation in prompting increased ZR activity. We also discuss whether neural DHEA[S] synthesis is coordinately regulated with the developing adrenal gland. We propose that DHEA[S] is crucial in the brain maturation of humans prior to and during puberty, and suggest that the function of the adrenarche is to modulate, adapt and rewire the pre-adolescent brain for new and ever-changing social challenges. The etiology of DHEA[S] synthesis, neurodevelopment and recently described 11-keto and 11-oxygenated androgens are difficult to investigate in humans owing to: (i) ethical restrictions on mechanistic studies, (ii) the inability to predict which individuals will develop specific mental characteristics, and (iii) the difficulty of conducting retrospective studies based on perinatal complications. We discuss new opportunities for animal studies to overcome these important issues.
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18

Jang, Seung-Ho, Young Sup Woo, Sang-Yeol Lee, and Won-Myong Bahk. "The Brain–Gut–Microbiome Axis in Psychiatry." International Journal of Molecular Sciences 21, no. 19 (September 27, 2020): 7122. http://dx.doi.org/10.3390/ijms21197122.

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Beginning with the concept of the brain–gut axis, the importance of the interaction between the brain and the gastrointestinal tract has been extended to the microbiome with increasing clinical applications. With the recent development of various techniques for microbiome analysis, the number of relevant preclinical and clinical studies on animals and human subjects has rapidly increased. Various psychotic symptoms affect the intestinal microbiome through the hypothalamus–pituitary–adrenal gland axis. Conversely, the intestinal microbiome regulates the gastrointestinal tract environment and affects psychological factors by means of the microorganisms or their metabolites, either acting directly on the brain or through the synthesis of various neurotransmitters. This review discusses the clinical applicability of the brain–gut–microbiome axis and directions for improving psychological symptoms based on the studies published to date.
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19

Hollander-Cohen, Lian, Matan Golan, and Berta Levavi-Sivan. "Differential Regulation of Gonadotropins as Revealed by Transcriptomes of Distinct LH and FSH Cells of Fish Pituitary." International Journal of Molecular Sciences 22, no. 12 (June 17, 2021): 6478. http://dx.doi.org/10.3390/ijms22126478.

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From mammals to fish, reproduction is driven by luteinizing hormone (LH) and follicle-stimulating hormone (FSH) temporally secreted from the pituitary gland. Teleost fish are an excellent model for addressing the unique regulation and function of each gonadotropin cell since, unlike mammals, they synthesize and secrete LH and FSH from distinct cells. Only very distant vertebrate classes (such as fish and birds) demonstrate the mono-hormonal strategy, suggesting a potential convergent evolution. Cell-specific transcriptome analysis of double-labeled transgenic tilapia expressing GFP and RFP in LH or FSH cells, respectively, yielded genes specifically enriched in each cell type, revealing differences in hormone regulation, receptor expression, cell signaling, and electrical properties. Each cell type expresses a unique GPCR signature that reveals the direct regulation of metabolic and homeostatic hormones. Comparing these novel transcriptomes to that of rat gonadotrophs revealed conserved genes that might specifically contribute to each gonadotropin activity in mammals, suggesting conserved mechanisms controlling the differential regulation of gonadotropins in vertebrates.
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Ząbczyńska, Marta, Kamila Kozłowska, and Ewa Pocheć. "Glycosylation in the Thyroid Gland: Vital Aspects of Glycoprotein Function in Thyrocyte Physiology and Thyroid Disorders." International Journal of Molecular Sciences 19, no. 9 (September 17, 2018): 2792. http://dx.doi.org/10.3390/ijms19092792.

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The key proteins responsible for hormone synthesis in the thyroid are glycosylated. Oligosaccharides strongly affect the function of glycosylated proteins. Both thyroid-stimulating hormone (TSH) secreted by the pituitary gland and TSH receptors on the surface of thyrocytes contain N-glycans, which are crucial to their proper activity. Thyroglobulin (Tg), the protein backbone for synthesis of thyroid hormones, is a heavily N-glycosylated protein, containing 20 putative N-glycosylated sites. N-oligosaccharides play a role in Tg transport into the follicular lumen, where thyroid hormones are produced, and into thyrocytes, where hyposialylated Tg is degraded. N-glycans of the cell membrane transporters sodium/iodide symporter and pendrin are necessary for iodide transport. Some changes in glycosylation result in abnormal activity of the thyroid and alteration of the metabolic clearance rate of hormones. Alteration of glycan structures is a pathological process related to the progression of chronic diseases such as thyroid cancers and autoimmunity. Thyroid carcinogenesis is accompanied by changes in sialylation and fucosylation, β1,6-branching of glycans, the content and structure of poly-LacNAc chains, as well as O-GlcNAcylation, while in thyroid autoimmunity the main processes affected are sialylation and fucosylation. The glycobiology of the thyroid gland is an intensively studied field of research, providing new data helpful in understanding the role of the sugar component in thyroid protein biology and disorders.
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21

ZAKI, M., A. MASSOUD, G. MADKOUR, N. EL-FIKY, and J. EL-MESIRY. "The Cyclic Changes in the Pituitary Gland and Gonads of Siganus rivulatus from the Red Sea (Hurghada Area)." Journal of King Abdulaziz University-Marine Sciences 7, no. 1 (1996): 271–84. http://dx.doi.org/10.4197/mar.7-1.24.

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22

Wojtulewicz, Karolina, Agata Krawczyńska, Dorota Tomaszewska-Zaremba, Maciej Wójcik, and Andrzej P. Herman. "Effect of Acute and Prolonged Inflammation on the Gene Expression of Proinflammatory Cytokines and Their Receptors in the Anterior Pituitary Gland of Ewes." International Journal of Molecular Sciences 21, no. 18 (September 21, 2020): 6939. http://dx.doi.org/10.3390/ijms21186939.

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An acute and prolonged inflammation inhibits the reproduction process by the disruption of the neurohormonal activity of the hypothalamic-pituitary-gonadal axis. It is thought that these changes may be caused by proinflammatory cytokines, i.e., interleukin (IL) -1β, IL-6 and tumor necrosis factor (TNF) α. The aim of this study was to determine the effect of an acute and prolonged inflammation on the expression of genes encoding cytokine and their receptors, gonadotropin releasing hormone receptor (GnRHR), beta subunits of luteinizing hormone (LHβ) and follicle-stimulating (FSHβ) in the anterior pituitary (AP). Moreover, the circulating concentration of LH and FSH was also assayed. Two experiments were carried out on adult ewes which were divided into two control groups and treated with lipopolysaccharide (LPS; 400 ng / kg). Acute inflammation was caused by a single injection of LPS into the external jugular vein, while the chronic inflammation was induced by seven times LPS injection (one a day). In both experiments, animals were euthanized 3h after the last LPS / NaCl injection and the blood samples collected 15 min before euthanasia. An acute inflammation stimulates the expression of the IL-1β, IL-6 and TNFα genes and their receptors in the AP of sheep. Prolonged inflammation increased TNFα gene expression and both types of TNFα and IL-6 receptors. Both an acute and prolonged inflammation inhibited LHβ gene expression in the AP and reduced LH level in blood. A sevenfold LPS injection raises FSH concentration. The gene expression of GnRHR was reduced in the ovine AP only after a single injection of endotoxin. Our results suggest that there are important differences in the way how an acute and prolonged inflammation influence proinflammatory cytokines and their receptors gene expression in the AP of anestrous ewes, which could be reflected by differences in the AP secretory activity during these states.
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Nurlaili, Nurlaili. "MENOPAUSE DAN PENGARUHNYA DALAM KEHIDUPAN PERKAWINAN." Marwah: Jurnal Perempuan, Agama dan Jender 11, no. 2 (November 2, 2012): 1. http://dx.doi.org/10.24014/marwah.v11i2.509.

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Menopause occurs exactly at the end of the last menstrual cycle, but the new certainty is obtained if a woman has not experienced the cycle for at least 12 months. When the levels of estrogen and progesterone decline, the hypothalamus and the pituitary gland trying to correct it and this leads to disruption of the normal operation of other body systems, including metabolism, brain chemistry, and bone conditions. The resulting changes include changes in the physical and psychological conditions are very individual (there are experienced and some not). Common physical changes experienced by menopausal women include: skin wrinkles or loosened, urinary incontinence (urinary control disorders), heart palpitations during activity, body temperature increases abruptly, headache, and easy to forget. While the changes in psychological conditions often lead to feelings of depression, and quick to anger. In addition it is the threat of osteoporosis (bone loss), which makes easy fractures impaired calcium absorption and poses a risk of cardiovascular disorders that contribute to raise the risk of heart disease and stroke.
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Zulueta, Benjamin C. "Master of the Master Gland: Choh Hao Li, the University of California, and Science, Migration, and Race." Historical Studies in the Natural Sciences 39, no. 2 (2009): 129–70. http://dx.doi.org/10.1525/hsns.2009.39.2.129.

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This essay examines the origins of the relationship between Choh Hao Li and the University of California, Berkeley. Li came to the United States from China in 1935 for graduate study at the University of Michigan, but ended up enrolling at Berkeley. Over the course of the next two decades, Li went from being a foreign graduate student in chemistry on a temporary visa to an internationally recognized leader in the biochemistry of endocrinology at the head of his own laboratory and a naturalized citizen of the United States. At what was otherwise a dark time for Americans of Chinese descent, Li was garnering adulation in the popular press. He was called the "master of the master gland" for his successes both in isolating and in synthesizing pituitary hormones. Specifically, the essay explores the making of the "master of the master gland" from the perspectives of the history of science and the history of race and migration in the United States, tracing the interplay among Li's scientific work, his migrations, his career aspirations, and his legal status in the United States. A Chinese intellectual cast adrift by the shifting geopolitics of World War II and the early Cold War, Li danced delicately along the margins of membership in American society during the 1940s, only arriving at what turned out to be his final destination after careful and protracted negotiations with officials of the U.S. government, with influential members of the international scientific community, and with representatives of the University of California, Berkeley.
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25

Recchia, Kaiana, Amanda Soares Jorge, Laís Vicari de Figueiredo Pessôa, Ramon Cesar Botigelli, Vanessa Cristiane Zugaib, Aline Fernanda de Souza, Daniele dos Santos Martins, Carlos Eduardo Ambrósio, Fabiana Fernandes Bressan, and Naira Caroline Godoy Pieri. "Actions and Roles of FSH in Germinative Cells." International Journal of Molecular Sciences 22, no. 18 (September 18, 2021): 10110. http://dx.doi.org/10.3390/ijms221810110.

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Follicle stimulating hormone (FSH) is produced by the pituitary gland in a coordinated hypothalamic–pituitary–gonadal (HPG) axis event, plays important roles in reproduction and germ cell development during different phases of reproductive development (fetal, neonatal, puberty, and adult life), and is consequently essential for fertility. FSH is a heterodimeric glycoprotein hormone of two dissociable subunits, α and β. The FSH β-subunit (FSHβ) function starts upon coupling to its specific receptor: follicle-stimulating hormone receptor (FSHR). FSHRs are localized mainly on the surface of target cells on the testis and ovary (granulosa and Sertoli cells) and have recently been found in testicular stem cells and extra-gonadal tissue. Several reproduction disorders are associated with absent or low FSH secretion, with mutation of the FSH β-subunit or the FSH receptor, and/or its signaling pathways. However, the influence of FSH on germ cells is still poorly understood; some studies have suggested that this hormone also plays a determinant role in the self-renewal of germinative cells and acts to increase undifferentiated spermatogonia proliferation. In addition, in vitro, together with other factors, it assists the process of differentiation of primordial germ cells (PGCLCs) into gametes (oocyte-like and SSCLCs). In this review, we describe relevant research on the influence of FSH on spermatogenesis and folliculogenesis, mainly in the germ cell of humans and other species. The possible roles of FSH in germ cell generation in vitro are also presented.
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Jindatip, Depicha, Rebecca Wan-Yan Poh, and Ken Fujiwara. "Insight into the Characteristics of Novel Desmin-Immunopositive Perivascular Cells of the Anterior Pituitary Gland Using Transmission and Focused Ion Beam Scanning Electron Microscopy." International Journal of Molecular Sciences 22, no. 16 (August 11, 2021): 8630. http://dx.doi.org/10.3390/ijms22168630.

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Recently, another new cell type was found in the perivascular space called a novel desmin-immunopositive perivascular (DIP) cell. However, the differences between this novel cell type and other nonhormone-producing cells have not been clarified. Therefore, we introduced several microscopic techniques to gain insight into the morphological characteristics of this novel DIP cell. We succeeded in identifying novel DIP cells under light microscopy using desmin immunocryosection, combining resin embedding blocks and immunoelectron microscopy. In conventional transmission electron microscopy, folliculostellate cells, capsular fibroblasts, macrophages, and pericytes presented a flat cisternae of rough endoplasmic reticulum, whereas those of novel DIP cells had a dilated pattern. The number of novel DIP cells was greatest in the intact rats, though nearly disappeared under prolactinoma conditions. Additionally, focused ion beam scanning electron microscopy showed that these novel DIP cells had multidirectional processes and some processes reached the capillary, but these processes did not tightly wrap the vessel, as is the case with pericytes. Interestingly, we found that the rough endoplasmic reticulum was globular and dispersed throughout the cytoplasmic processes after three-dimensional reconstruction. This study clearly confirms that novel DIP cells are a new cell type in the rat anterior pituitary gland, with unique characteristics.
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27

Izzi-Engbeaya, Chioma, Ali Abbara, Anthony Cass, and Waljit Dhillo. "Using Aptamers as a Novel Method for Determining GnRH/LH Pulsatility." International Journal of Molecular Sciences 21, no. 19 (October 7, 2020): 7394. http://dx.doi.org/10.3390/ijms21197394.

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Aptamers are a novel technology enabling the continuous measurement of analytes in blood and other body compartments, without the need for repeated sampling and the associated reagent costs of traditional antibody-based methodologies. Aptamers are short single-stranded synthetic RNA or DNA that recognise and bind to specific targets. The conformational changes that can occur upon aptamer–ligand binding are transformed into chemical, fluorescent, colour changes and other readouts. Aptamers have been developed to detect and measure a variety of targets in vitro and in vivo. Gonadotropin-releasing hormone (GnRH) is a pulsatile hypothalamic hormone that is essential for normal fertility but difficult to measure in the peripheral circulation. However, pulsatile GnRH release results in pulsatile luteinizing hormone (LH) release from the pituitary gland. As such, LH pulsatility is the clinical gold standard method to determine GnRH pulsatility in humans. Aptamers have recently been shown to successfully bind to and measure GnRH and LH, and this review will focus on this specific area. However, due to the adaptability of aptamers, and their suitability for incorporation into portable devices, aptamer-based technology is likely to be used more widely in the future.
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Ide, Veerle, Dirk Vanderschueren, and Leen Antonio. "Treatment of Men with Central Hypogonadism: Alternatives for Testosterone Replacement Therapy." International Journal of Molecular Sciences 22, no. 1 (December 22, 2020): 21. http://dx.doi.org/10.3390/ijms22010021.

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Central hypogonadism is a clinical condition, characterized by sexual symptoms and low serum testosterone levels, due to an impaired function of the hypothalamus or pituitary gland. Testosterone replacement therapy (TRT) is the standard treatment for hypogonadism, but it has some disadvantages. TRT is not a good option in men wishing to preserve fertility, nor in men with (a high risk of) prostate cancer, polycythemia, thrombophilia and severe cardiovascular disease. In this review, we discuss alternative treatments for central hypogonadism. If reversible causes are present, non-pharmacological interventions can be therapeutic. Gonadotropins are a good alternative to TRT when fertility is desired in the near future though they require frequent injections. Clomiphene citrate and tamoxifen seem to be a safe alternative for the treatment of functional central hypogonadism in men, as several studies reported a significant increase in testosterone levels with these drugs. However, their use is off-label and data supporting the efficacy of clomiphene citrate and tamoxifen on hypogonadal symptoms are insufficient. For this reason, clomiphene citrate and tamoxifen should not be used in routine clinical practice to treat sexual symptoms in men with central hypogonadism.
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Siemiradzka, Wioletta, Barbara Dolińska, and Florian Ryszka. "Development and Study of Semi-Solid Preparations Containing the Model Substance Corticotropin (ACTH): Convenience Application in Neurodegenerative Diseases." Molecules 25, no. 8 (April 16, 2020): 1824. http://dx.doi.org/10.3390/molecules25081824.

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Corticotropin (ACTH, previously an adrenocorticotropic hormone) is used in the diagnosis and treatment of pituitary gland disorders, adrenal cortex disorders, and other diseases, including autoimmune polymyositis, systemic lupus erythematosus, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis. So far, the ointment dosage form containing ACTH for use on the skin is unknown. Therefore, it seems appropriate to develop a semi-solid formulation with corticotropin. Emulsion ointments were prepared using an Unguator based on the cream base Lekobaza® containing corticotropin in different concentrations, and then the physical and chemical parameters of the ointment formulations, such as pH, spreadability, rheological properties, and texture analysis, were evaluated. In addition, a USP apparatus 2 with enhancer cells was utilized to study the in vitro drug release characteristics of the selected formulations. All the ointments obtained were characterized by good spreadability and viscosity. An analysis of the ointment texture was performed and the dependence of the tested parameters on the ACTH content in the ointment was demonstrated. Examination of the structure of the ointment showed that a high concentration of ACTH increases the hardness and adhesiveness of the ointment. In turn, it adversely affects the cohesiveness and elasticity of the ointments tested. The results of the release study showed that ACTH is released the fastest from the formulation with the lowest concentration, while the slowest from the ointment with the highest concentration of ACTH.
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30

Rijal, Santosh, Dong Hyu Cho, Seon-Ah Park, Seon Hui Jang, István M. Ábrahám, and Seong Kyu Han. "Melatonin Suppresses the Kainate Receptor-Mediated Excitation on Gonadotropin-Releasing Hormone Neurons in Female and Male Prepubertal Mice." International Journal of Molecular Sciences 21, no. 17 (August 20, 2020): 5991. http://dx.doi.org/10.3390/ijms21175991.

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Melatonin, a pineal gland secretion, is an amphiphilic neurohormone involved in the biological and physiologic regulation of bodily functions. Numerous studies have shown the effects of melatonin on the release of gonadotropins and their actions at one or several levels of the hypothalamic–pituitary–gonadal axis. However, direct melatonin action on gonadotropin-releasing hormone (GnRH) neurons and its mechanism of action remain unclear. Here, plasma melatonin levels were measured and the effect of melatonin on GnRH neurons was assessed using brain slice patch clamp techniques. The plasma melatonin levels in prepubertal mice were higher than those in the adults. Melatonin itself did not change the firing activity of GnRH neurons. Interestingly, the kainate receptor-mediated responses but not the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N-methyl-D-aspartic acid (NMDA)-induced responses were suppressed by melatonin in both the voltage clamp and current clamp modes. The inhibitory effects of the kainate-induced response by melatonin tended to increase with higher melatonin concentrations and persisted in the presence of tetrodotoxin, a voltage-sensitive Na+ channel blocker, or luzindole, a non-selective melatonin receptor antagonist. However, the response was completely abolished by pretreatment with pertussis toxin. These results suggest that melatonin can regulate GnRH neuronal activities in prepubertal mice by partially suppressing the excitatory signaling mediated by kainate receptors through pertussis toxin-sensitive G-protein-coupled receptors.
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31

Freyberger, A., Peter Andrews, Elke Hartmann, Rolf Eiben, Ingo Loof, U. Schmidt, M. Temerowski, et al. "Testing of endocrine active substances using an enhanced OECD test guideline 407: Experiences from studies on flutamide and ethinylestradiol." Pure and Applied Chemistry 75, no. 11-12 (January 1, 2003): 2483–89. http://dx.doi.org/10.1351/pac200375112483.

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Groups of five male and five female Wistar rats were treated by gavage with 0, 1, 10, and 100 mg/kg body weight (b.w.) flutamide (FLU) or 0.01, 0.05, and 0.2 mg/kg b.w. of ethinylestradiol (EE2) for at least 28 days according to an enhanced Organization for Economic Cooperation and Development (OECD) test guideline (TG) 407 to investigate which of the current and/or additional parameters would detect effects on the endocrine system and to provide data on intralaboratory variability. Two identical studies were performed in parallel on each compound. Common enhancements were determination of thyroid hormones (T3, T4) and thyroid stimulating hormone (TSH), of the stage of the estric cycle to ensure necropsy of females in diestrus, of the number and morphology of epididymal sperm, and of additional organ weights (e.g., male accessory sex organs, MASO) and histopathology of additional organs (e.g., pituitary, vagina). Endocrine-mediated findings consistently observed in these studies were decreased relative weights of MASO at 100 mg/kg FLU and at 0.2 mg/kg EE2, histological changes in pituitary and testes at &gt; or = 10 mg/kg and in MASO, epididymis and adrenals at 100 mg/kg in FLU-treated males, histological changes in the mammary gland at &gt; or = 0.05 mg/kg and in testes, MASO and adrenals at 0.2 mg/kg in EE2-treated males, estrogenization of uterus and vagina (despite necropsy in diestrus) at &gt; or = 0.01 mg/kg EE2, and changes in the ovary at 0.2 mg/kg EE2. Spermatology was insensitive (EE2) or revealed changes only at the maximum tolerated dose (MTD). Determination of T3, T4, and TSH did not contribute to the detection of the endocrine effects (FLU) or provided equivocal results. Doubling the group size to 10 animals by combining the studies run in parallel did not increase the sensitivity of detection of endocrine-mediated effects above the level obtained by histopathological examination of groups of five animals. Only some of the proposed enhancements evaluated were helpful in detecting the endocrine-mediated effects of FLU and EE2. Evaluation of studies according to an enhanced TG 407 on 10 compounds with different endocrine activities will identify the most appropriate enhancements.
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Venugopalan, Vaishnavi, Alaa Al-Hashimi, Maren Rehders, Janine Golchert, Vivien Reinecke, Georg Homuth, Uwe Völker, et al. "The Thyroid Hormone Transporter Mct8 Restricts Cathepsin-Mediated Thyroglobulin Processing in Male Mice through Thyroid Auto-Regulatory Mechanisms That Encompass Autophagy." International Journal of Molecular Sciences 22, no. 1 (January 5, 2021): 462. http://dx.doi.org/10.3390/ijms22010462.

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The thyroid gland is both a thyroid hormone (TH) generating as well as a TH responsive organ. It is hence crucial that cathepsin-mediated proteolytic cleavage of the precursor thyroglobulin is regulated and integrated with the subsequent export of TH into the blood circulation, which is enabled by TH transporters such as monocarboxylate transporters Mct8 and Mct10. Previously, we showed that cathepsin K-deficient mice exhibit the phenomenon of functional compensation through cathepsin L upregulation, which is independent of the canonical hypothalamus-pituitary-thyroid axis, thus, due to auto-regulation. Since these animals also feature enhanced Mct8 expression, we aimed to understand if TH transporters are part of the thyroid auto-regulatory mechanisms. Therefore, we analyzed phenotypic differences in thyroid function arising from combined cathepsin K and TH transporter deficiencies, i.e., in Ctsk-/-/Mct10-/-, Ctsk-/-/Mct8-/y, and Ctsk-/-/Mct8-/y/Mct10-/-. Despite the impaired TH export, thyroglobulin degradation was enhanced in the mice lacking Mct8, particularly in the triple-deficient genotype, due to increased cathepsin amounts and enhanced cysteine peptidase activities, leading to ongoing thyroglobulin proteolysis for TH liberation, eventually causing self-thyrotoxic thyroid states. The increased cathepsin amounts were a consequence of autophagy-mediated lysosomal biogenesis that is possibly triggered due to the stress accompanying intrathyroidal TH accumulation, in particular in the Ctsk-/-/Mct8-/y/Mct10-/- animals. Collectively, our data points to the notion that the absence of cathepsin K and Mct8 leads to excessive thyroglobulin degradation and TH liberation in a non-classical pathway of thyroid auto-regulation.
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33

Miller, Walter L. "The Hypothalamic-Pituitary-Adrenal Axis: A Brief History." Hormone Research in Paediatrics 89, no. 4 (2018): 212–23. http://dx.doi.org/10.1159/000487755.

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The hypothalamic-pituitary-adrenal (HPA) axis is central to homeostasis, stress responses, energy metabolism, and neuropsychiatric function. The history of this complex system involves discovery of the relevant glands (adrenal, pituitary, hypothalamus), hormones (cortisol, corticotropin, corticotropin-releasing hormone), and the receptors for these hormones. The adrenal and pituitary were identified by classical anatomists, but most of this history has taken place rather recently, and has involved complex chemistry, biochemistry, genetics, and clinical investigation. The integration of the HPA axis with modern neurology and psychiatry has cemented the role of endocrinology in contemporary studies of behavior.
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34

Perkinson, Michael R., Rachael A. Augustine, Gregory T. Bouwer, Emily F. Brown, Isaiah Cheong, Alexander J. Seymour, Martin Fronius, and Colin H. Brown. "Plasticity in Intrinsic Excitability of Hypothalamic Magnocellular Neurosecretory Neurons in Late-Pregnant and Lactating Rats." International Journal of Molecular Sciences 22, no. 13 (July 1, 2021): 7140. http://dx.doi.org/10.3390/ijms22137140.

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Oxytocin and vasopressin secretion from the posterior pituitary gland are required for normal pregnancy and lactation. Oxytocin secretion is relatively low and constant under basal conditions but becomes pulsatile during birth and lactation to stimulate episodic contraction of the uterus for delivery of the fetus and milk ejection during suckling. Vasopressin secretion is maintained in pregnancy and lactation despite reduced osmolality (the principal stimulus for vasopressin secretion) to increase water retention to cope with the cardiovascular demands of pregnancy and lactation. Oxytocin and vasopressin secretion are determined by the action potential (spike) firing of magnocellular neurosecretory neurons of the hypothalamic supraoptic and paraventricular nuclei. In addition to synaptic input activity, spike firing depends on intrinsic excitability conferred by the suite of channels expressed by the neurons. Therefore, we analysed oxytocin and vasopressin neuron activity in anaesthetised non-pregnant, late-pregnant, and lactating rats to test the hypothesis that intrinsic excitability of oxytocin and vasopressin neurons is increased in late pregnancy and lactation to promote oxytocin and vasopressin secretion required for successful pregnancy and lactation. Hazard analysis of spike firing revealed a higher incidence of post-spike hyperexcitability immediately following each spike in oxytocin neurons, but not in vasopressin neurons, in late pregnancy and lactation, which is expected to facilitate high frequency firing during bursts. Despite lower osmolality in late-pregnant and lactating rats, vasopressin neuron activity was not different between non-pregnant, late-pregnant, and lactating rats, and blockade of osmosensitive ΔN-TRPV1 channels inhibited vasopressin neurons to a similar extent in non-pregnant, late-pregnant, and lactating rats. Furthermore, supraoptic nucleus ΔN-TRPV1 mRNA expression was not different between non-pregnant and late-pregnant rats, suggesting that sustained activity of ΔN-TRPV1 channels might maintain vasopressin neuron activity to increase water retention during pregnancy and lactation.
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35

Fukushima, S., and A. Freyberger. "Simple, rapid assays for conventional definite testing of endocrine disruptor hazard: Summary and recommendations." Pure and Applied Chemistry 75, no. 11-12 (January 1, 2003): 2479–82. http://dx.doi.org/10.1351/pac200375112479.

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Study protocols for the characterization of endocrine active compounds presented in Workshop 4 included the enhanced Organization for Economic Cooperation and Development (OECD) test guideline (TG) 407, the medium-term rat liver and rat multi-organ carcinogenicity assays, and an enhanced one-generation reproduction study. The outcome of rat studies on flutamide and ethinylestradiol indicated that these strongly active compounds can readily be detected even with a low animal number using the enhanced OECD TG 407. Both newly added (such as male accessory sex organ weights, histology of pituitary, vagina and male mammary gland) and already included parameters contributed to the detection of endocrine effects. Thorough evaluation of the results of 20 studies conducted with 10 compounds thought to interfere with the endocrine system by different mechanisms will identify the most appropriate enhancements to the current OECD TG 407. Medium-term rat liver and rat multi-organ carcinogenicity assays are well recognized in the International Conferences on Harmonization for Pharmaceutical Chemicals. They have been successfully used to detect carcinogenic and modifying potentials of new chemicals within a relatively short time and can be applied to endocrine active compounds. Dose-response studies on nonylphenol, bisphenol A, and styrene using the rat liver carcinogenicity assay did not reveal effects of any of these compounds on the development of preneoplastic lesions in rat liver. The enhanced one-generation reproduction study protocol included treatment of pregnant female rats from gestation day 0 through to lactation day 21, and examination of all offspring. Half of the animals were necropsied at weaning, the remaining animals were examined for vaginal opening, preputial separation, estrous cyclicity, and sperm characteristics and were necropsied at adulthood. In a pilot study ethinylestradiol inhibited maternal fertility at dose levels similar to those effective in the uterotrophic assay. It is recommended to rapidly evaluate the conducted enhanced OECD TG 407 studies and to enhance the current OECD TG 407 appropriately. Further compounds with different mechanisms of action should be studied in the one-generation reproduction study to further investigate the usefulness of this protocol. The established medium-term carcinogenicity assays can be used to study carcinogenic potential rapidly. Use of female animals and inclusion of carcinogens targeting at breast and uterus should be considered in order to explore further the predictibility of this model.
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36

De Castro, Alicia, Richard J. Comi, Andrew Robert Crawford, Natasa Radovanovic, Hima Ammana, and Leigh Kwak. "An Unusual Case of Bilateral Adrenal Hyperplasia." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A116. http://dx.doi.org/10.1210/jendso/bvab048.233.

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Abstract Background: Thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly (TAFRO) syndrome is a variant of Castleman Disease, which is a rare lymphoproliferative disease that can be life threatening. Diagnosis is often delayed because of its nonspecific presentation. Bilateral adrenal hyperplasia has been a reported complication, however the majority of cases reported have been in Asian patients. Prior accounts of elevated ACTH in TAFRO have been in the context of adrenal insufficiency. Clinical Case: A 28-year-old Caucasian male with a history of multiple sclerosis was seen in the ED with abdominal pain. On presentation, he was afebrile and normotensive. Physical exam was notable for cervical lymphadenopathy and abdominal tenderness. There was no facial rounding/plethora, bruising, abnormal striae, or proximal muscle weakness. He had normal blood counts, serum chemistry and liver function. An abdominal CT scan showed marked bilateral adrenal hyperplasia with pre-aortic, peri-aortic and retroperitoneal lymphadenopathy. An 8AM serum cortisol was 14.1 mcg/dl (4.8–19.6 mcg/dl) and adrenocorticotrophic hormone (ACTH) was elevated at 152 pg/ml (7.2–63 pg/ml). A repeat serum 8AM cortisol following low dose dexamethasone suppression test (LDDST) was 14.7 mcg/dl, however at that point the patient had developed new fevers and thrombocytopenia. Blood pressure, blood glucose and potassium remained normal. An MRI of the brain showed a normal appearing pituitary gland. An extensive infectious and rheumatologic evaluation was negative, and he underwent an inguinal lymph node biopsy which showed nodal expansion with histiocytes, consistent with TAFRO. High dose methylprednisolone and Siltuximab (an IL-6 inhibitor) were started, and his fever and abdominal pain resolved. He was discharged home on oral prednisone. Conclusion: We describe a case of bilateral adrenal hyperplasia with elevated ACTH and non-suppressed cortisol on LDDST suggestive of ACTH-driven cortisol excess. However, interpretation of his LDDST is made difficult in the context of persistent fevers. Although we cannot definitively exclude pathologic hypercortisolism at this time, given his lack of suggestive features such as proximal muscle weakness, abnormal striae or hypokalemic alkalosis, his over-all presentation was more consistent with hyperplasia secondary to TAFRO rather than an underlying pathologic hypercortisolism. Adrenal hyperplasia has been noted in TAFRO, however its pathogenesis remains poorly understood. TAFRO should be added among the differentials for bilateral adrenal hyperplasia to facilitate early diagnosis and treatment. References: Ducoux G, et al. Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis/Renal Failure, and Organomegaly (TAFRO) Syndrome with Bilateral Adrenal Hemorrhage in Two Caucasian Patients. Am J Case Rep. 2020;21:e919536.
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37

Cornett, C. R., W. D. Ehmann, D. R. Wekstein, and W. R. Markesbery. "Trace elements in Alzheimer's disease pituitary glands." Biological Trace Element Research 62, no. 1-2 (April 1998): 107–14. http://dx.doi.org/10.1007/bf02820026.

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38

Pérez, Pablo A., Jonathan Toledo, Liliana del Valle Sosa, Nahuel Peinetti, Alicia I. Torres, Ana L. De Paul, and Silvina Gutiérrez. "The phthalate DEHP modulates the estrogen receptors α and β increasing lactotroph cell population in female pituitary glands." Chemosphere 258 (November 2020): 127304. http://dx.doi.org/10.1016/j.chemosphere.2020.127304.

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39

Basalaeva, Nadezdha L. "Iodine-Induced Thyroid Blockade: Role of Selenium and Iodine in the Thyroid and Pituitary Glands." Biological Trace Element Research 154, no. 2 (June 16, 2013): 244–54. http://dx.doi.org/10.1007/s12011-013-9708-6.

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40

Kese, Anamaria, Mihai Constantin Razvan Barbu, Denisa Enescu Bieru, Dumitru Barbu, Sorin Berbece, and Doru Stoica. "The Role of Non-Pharmacological Treatment for Osteoporosis at Patients with High Plasmatic Concentration of ACTH." Revista de Chimie 71, no. 1 (February 7, 2020): 254–58. http://dx.doi.org/10.37358/rc.20.1.7842.

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Cushing disease is characterized by the hypersecretion of adrenocorticotropic hormone (ACTH) due to a pituitary adenoma that causes endogenous hypercortisolism by stimulating adrenal glands. Objective of the study was to analyse the benefits of the physical therapy for patients with ACTH-secreting adenomas osteoporosis.This retrospective study was performed at Craiova, Bunavestire Hospital, the patients were monitorized during 6 months and included 17 patients with ACTH-secretingadenomas. Participants in this study group exercised 3 days a week for 6 consecutive months. Each session is intended to take approximately 60 minutes to complete and will comprise of a warm-up, progressive resistance training using medium weights, moderate impact weight-bearing exercises, flexibility and also stretching exercises. Physical therapy for osteoporosis treatment in patients with ACTH-secreting adenomas improved joint mobility and reduced pain, significantly increasing BMD performed by DEXA in group I patients compared to patients included in group II. Pain relief is evident following evaluation using the VAS rating scale. The increase in joint mobility is observed following the goniometric measurement from day 1 to the end of treatment. Applying the physical therapy program the bone pain and joint mobility was improved, physical therapy can modify bone turnover in the sense of increasing the body mass.
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41

Pohar, Michael, and Nils Hansson. "Between two stools? Pharmacologists nominated for Nobel prizes in “physiology or medicine” and “chemistry” 1901–1950 with a focus on John Jacob Abel (1857–1938)." Naunyn-Schmiedeberg's Archives of Pharmacology, October 15, 2020. http://dx.doi.org/10.1007/s00210-020-01993-0.

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Abstract Since the early stages of its academic professionalization, pharmacology has been an interdisciplinary field strongly influenced by the natural sciences. Using the Nobel Prize as a lens to study the history of pharmacology, this article analyzes nominations of pharmacologists for two Nobel Prize categories, namely “chemistry” and “physiology or medicine” from 1901 to 1950. Who were they? Why were they proposed, and what do the Nobel dossiers say about excellence in pharmacology and research trends? This paper highlights the evaluation of “shortlisted” candidates, i.e., those candidates who were of particular interest for the members of the Nobel Committee in physiology or medicine. We focus on the US scholar John Jacob Abel (1857–1938), repeatedly referred to as the “Founder of American Pharmacology.” Nominated 17 times in both categories, Abel was praised by his nominators for both basic research as well as for his influential positions as editor and his work as chair at Johns Hopkins University. The Abel nominations were evaluated for the Nobel Committee in chemistry by the Swedish professor of chemistry and pharmaceutics Einar Hammarsten (1889–1968), particularly interested in Abel’s work on hormones in the adrenal glands and in the pituitary gland. Eventually, Hammarsten did not view Abel’s work prizeworthy, partly because other scholars had done—according to Hammarsten—more important discoveries in the same fields. In conclusion, analyses of Nobel Prize nominations help us to better understand various meanings of excellence in pharmacology during the twentieth century and beyond.
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Zhang, Shu, Yueli Cui, Xinyi Ma, Jun Yong, Liying Yan, Ming Yang, Jie Ren, Fuchou Tang, Lu Wen, and Jie Qiao. "Single-cell transcriptomics identifies divergent developmental lineage trajectories during human pituitary development." Nature Communications 11, no. 1 (October 19, 2020). http://dx.doi.org/10.1038/s41467-020-19012-4.

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Abstract The anterior pituitary gland plays a central role in regulating various physiological processes, including body growth, reproduction, metabolism and stress response. Here, we perform single-cell RNA-sequencing (scRNA-seq) of 4113 individual cells from human fetal pituitaries. We characterize divergent developmental trajectories with distinct transitional intermediate states in five hormone-producing cell lineages. Corticotropes exhibit an early intermediate state prior to full differentiation. Three cell types of the PIT-1 lineage (somatotropes, lactotropes and thyrotropes) segregate from a common progenitor coexpressing lineage-specific transcription factors of different sublineages. Gonadotropes experience two multistep developmental trajectories. Furthermore, we identify a fetal gonadotrope cell subtype expressing the primate-specific hormone chorionic gonadotropin. We also characterize the cellular heterogeneity of pituitary stem cells and identify a hybrid epithelial/mesenchymal state and an early-to-late state transition. Here, our results provide insights into the transcriptional landscape of human pituitary development, defining distinct cell substates and subtypes and illustrating transcription factor dynamics during cell fate commitment.
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Kusnetzow, Ana Karin, Sangdon Han, Melissa A. Fowler, Jon Athanacio, Greg Reinhart, Elizabeth Rico, Sun Hee Kim, et al. "MON-176 Discovery and Identification of Late Stage Selective Nonpeptide ACTH Antagonists for the Treatment of Cushing’s Disease, Ectopic ACTH Secreting Tumors, and Congenital Adrenal Hyperplasia." Journal of the Endocrine Society 4, Supplement_1 (April 2020). http://dx.doi.org/10.1210/jendso/bvaa046.690.

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Abstract Adrenocorticotropic hormone (ACTH) is an important modulator of steroidal hormone synthesis and secretion from the adrenal gland and its selective activity at the melanocortin type 2 receptor (MC2) dictates the synthesis and secretion of cortisol (corticosterone in rats). Excess ACTH action contribute to the pathophysiology of Cushing’s disease (CD), ectopic ACTH secreting tumors (EAS), and Congenital Adrenal Hyperplasia (CAH). Cushing’s disease results from a microadenoma derived from pituitary corticotrophic cells that secretes excess ACTH, whereas EAS arises from nonpituitary ACTH secreting tumors. Excess ACTH action at the adrenal gland and resulting hypercortisolemia presents in a myriad of symptoms that result in high morbidity. CAH results from inactivating mutations in steroid synthesis pathways, resulting in lack of cortisol and aldosterone production. Lack of negative feedback by cortisol at the level of the pituitary causes the over-secretion of ACTH, and overproduction of adrenal androgens, causing significant virilization and reduction in quality of life. We hypothesize that blocking ACTH action directly via a selective MC2 receptor antagonist may provide an important new therapeutic mechanism for these patients. To test this hypothesis, Crinetics launched an iterative medicinal chemistry program to identify potent and selective nonpeptide ACTH antagonists with pharmaceutical and safety characteristics suitable for evaluation in human clinical trials. Unlike most other G protein coupled receptors, MC2 requires the presence of an accessory protein (MRAP) for cell surface expression and recognition of ACTH. Using CHO-K cells stably expressing this MC2-MRAP complex, iterative optimization led to the discovery of multiple chemical classes of highly potent, nonpeptide MC2 receptor selective antagonist leads, which were then further optimized for drug-like characteristics. We identified multiple compounds that exhibit high potency for human and rat MC2 receptors (hMC2 Kb &lt;1 nM), while having no activity at the MC1, MC3, MC4, or MC5 receptors. Leading ACTH antagonists were also evaluated for drug like characteristics, including good stability in liver microsomes, lack of inhibition of cytochromes P450 and the hERG ion channel, and were shown to exhibit good exposure upon oral dosing in both rats and dogs. These ACTH antagonists acutely suppress corticosterone secretion in an ACTH-challenge model in rats. In a 7-day hypercortisolemia model in which rats receive an implanted minipump that continually secretes ACTH, corticosterone levels were decreased, and body weight loss and adrenal hypertrophy were prevented with ACTH antagonist treatment. The culmination of these studies has led to a subset of candidate molecules that are being evaluated in genotoxicity, safety pharmacology, and general toxicology studies to enable evaluation in human clinical trials.
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44

Kawaji, Leslie Daphne R., Mary Grace M. Villanueva, and Michael L. Villa. "SUN-276 Pembrolizumab-Induced Secondary Adrenal Insufficiency Presenting as Severe Hyponatremia in an 80-Year-Old Male." Journal of the Endocrine Society 4, Supplement_1 (April 2020). http://dx.doi.org/10.1210/jendso/bvaa046.703.

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Abstract Background Pembrolizumab is an anti-programmed death 1 (PD-1) antibody designed to incite an immune response against malignant cells. By virtue of this mechanism of action, its use has given rise to immune-related adverse events including those affecting the endocrine system. Adrenal insufficiency can occur rarely with anti-PD-1 therapy, and symptoms are usually non-specific. Clinical Case An 80-year-old male, known case of non-small cell lung cancer stage IV presented with a 2-week history of progressive body weakness with anorexia, shortness of breath and low-grade fever. He had just received the 4th cycle of pembrolizumab prior to the onset of symptoms. Past medical history was significant for hypertension and type 2 diabetes mellitus which were both controlled, and pulmonary tuberculosis with completed treatment. On physical examination, he was drowsy but oriented. He was normotensive (110/70 mmHg) and tachypneic (28 cpm) with rales on both lung fields. Baseline capillary glucose level was 107 mg/dL. Chest radiograph showed hazy opacities in the right upper to middle region. Blood chemistry revealed severe hyponatremia (114 mmol/L, NV 135-145 mmol/L) and low serum osmolality (247 mOsm/kg, NV 280-300 mOsm/kg). Random (taken 1230H) ACTH and cortisol were &lt;5.00 pg/mL (NV &lt;46 pg/mL) and 2.00 μg/dL (NV 4.30-22.40 μg/dL), respectively. Such levels were judged to be low in the background of an acute illness. Thyroid function tests were normal – TSH 0.993 μIU/mL (NV 0.55-4.78 uIU/mL), FT3 3.890 pg/mL (2.30-4.20 pg/mL), FT4 1.450 ng/dL (0.89-1.76 ng/dL). Magnetic resonance imaging of the pituitary gland did not show abnormal parenchymal enhancement or enlargement. Pembrolizumab-induced secondary adrenal insufficiency was the most probable cause of the hyponatremia. He was started on IV hydrocortisone, as well as piperacillin-tazobactam for pneumonia. Oxygen support via nasal cannula was given. Feeding via nasogastric tube was decided to ensure nutrition and prevent aspiration. He was transferred to the intensive care unit for careful monitoring. Serum sodium level was corrected gradually, with marked clinical improvement thereafter. Within 48 hours, he was transferred to regular room and oral feeding commenced. Hydrocortisone was shifted to prednisone on discharge, with steroid tapering schedule and close follow-up with endocrinologist advised. Conclusion We presented a case of secondary adrenal insufficiency which likely resulted from hypophysitis induced by pembrolizumab. Hypophysitis following anti-PD1 treatment occurs in &lt;1% of patients on immunotherapy. In such cases, ACTH deficiency is usually isolated and pituitary imaging is frequently normal. Since more patients are being placed on immune-checkpoint inhibition, clinicians should be vigilant for these adverse events, particularly the endocrinopathies which may have non-specific symptoms and may be irreversible.
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"Profiling protein expression in C. elegans | Metabolic monitoring of liver transplants | Isolating phosphopeptides with a dendrimer | Proteome of Trypanosoma cruzi | New protein immobilization technique | Early detection of ovarian cancer | Protein isoforms in serum vs. plasma | Protein losses in 2DE | Pituitary gland proteome." Journal of Proteome Research 4, no. 5 (October 2005): 1477–80. http://dx.doi.org/10.1021/pr050521r.

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46

Alkhaled, Lina, and Anzar Haider. "SAT-108 Growth Hormone Deficiency in a Patient with Ectodermal Dysplasia." Journal of the Endocrine Society 4, Supplement_1 (April 2020). http://dx.doi.org/10.1210/jendso/bvaa046.950.

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Abstract Background information: Ectodermal dysplasia (ED) is a rare heterogeneous group of genetic disorders of ectodermal derived tissues, characterized by abnormalities in skin, teeth, hair and eccrine glands. Growth failure in these children varies depending on the genetic mutation and has not been well characterized. This clinical case report presents a 11-year-old male with a heterozygous mutation in WNT 10 A, a variant of the hypohydrotic ED gene, who was found to have growth hormone (GH) deficiency and treated with GH. Case report: He was born at 35 weeks gestation by C-section with a birth weight of 5 lbs. 12 oz. to a mother who had invitro fertilization with donor eggs from the maternal aunt with ocular myasthenia gravis and sperm from the father. Pregnancy was complicated by twin gestation and polyhydraminos. He had transient myasthenia gravis and treated with pyridostigmine for 3 months for feeding problems and swallowing difficulty. He also had arthrogryposis of the distal upper extremities attributed to placental transfer of the maternal aunt’s myasthenia gravis antibodies. He was referred to the endocrine clinic for evaluation of his growth failure around the age of 8 years. His growth chart indicated that he grew along the 5thpercentile until age 5 year with a gradual decline to the 3rd percentile by age 7 year and close to 2nd percentile by age 8 year. His BMI was at 7th percentile. Mid parental height was 5’9”. There was no history of delayed adolescence in the family. His twin sister had very mild form of arthrogryposis with dental delay but steady linear growth. He also had decreased exercise tolerance. His body tended to become hot during sports activities and had to wrap his face and neck with cold soaked towels. His other problems included delayed dental development with conical incisor, thin nail, missing teeth and hearing defects that raised suspicion for ectodermal dysplasia. Genetic testing at the age of 4 years had demonstrated a heterozygous mutation in the WNT 10A gene, an important gene for tooth development. Physical examination revealed a mild facial dysmorphism with conical incisor, missing teeth and high arched palate. He had contracture of the proximal inter phalangeal joints of the hands. Investigations revealed a normal thyroid function test, IGF-1 and IGFBP-3 level, CBC, sedimentation rate, chemistry panel and celiac titer. The bone age was concordant with his chronological age of 8 years. A GH stimulation study demonstrated a peak GH level of 4.94 ng/ml. An MRI of the brain revealed a normal pituitary gland. He was started on GH therapy with 0.3 mg/kg/week at age 9 year. His height improved from 2nd percentile at age 9 year to 20th percentile by age 11 year on growth hormone therapy. His exercise capacity and stamina also improved. Conclusion: Growth failure and GH axis should be evaluated in children with ED. GH therapy improves growth velocity and exercise capacity in patients with ED.
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47

Ples, Liana, Cringu Ionescu, Mihai Dimitriu, Anca Lesnic, Zorela Adriana Sgarbura, and Alina Calin. "Is Ulipristal Acetate a Liver Toxic Biomolecule? Toxicity assessment of ulipristal acetate." Revista de Chimie 69, no. 8 (September 15, 2018). http://dx.doi.org/10.37358/rc.18.8.6456.

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Progesterone is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. Its main functions are playing a key role in the development, differentiation, and normal functioning of female reproduction-related target tissues including the uterus (endometrium and myometrium), the ovary, and the mammary gland, as well as regulating the hypothalamic�pituitary�gonadal axis. Soon after the discovery of the progesterone receptor (PR) it was appreciated that the development of a PR antagonist would have a major therapeutic potential. Numerous related compounds have been synthesized exhibiting a spectrum of activity ranging from pure progesterone receptor antagonists (PA), to mixed agonists/antagonists. These latter compounds are also known as selective progesterone receptor modulators (SPRM), progesterone receptor modulators (PRM), mesoprogestins or partial agonist�antagonists. Ulipristal acetate is a SPRM used in Europe for preoperative treatment of moderate-to-severe symptoms of uterine leiomyomas in adult women of reproductive age. This is a retrospective cohort study conducted in two medical units, Saint John Hospital and Egometacs Clinic, between january 2017-december 2018, on women treated with UPA (ulipristal acetate) for symptomatic uterine fibroids, in order to evaluate if there were any liver function changes after the treatment. In the mentioned period, 74 women were treated with UPA for symptomatic uterine myomas in the two units. After checking the records, 6 women were lost on follow up (only the first visit was recorded), 4 didn�t complete the treatment course and 7 had incomplete laboratory evaluation, either at the beginning or at the end of treatment. Finally, our cohort was comprised of 57 women, aged between 20 and 50 years old, treated with UPA for various conditions (myomas, abnormal bleeding, pelvic pain etc.) during a period of 3 month�, and adherence to treatment was 100%. We performed a paired T-test on the before and after values of the AST, ALT, GGT enzymes and total bilirubin levels, for our statistical analysis we used SPPS 20, and the charts were built using Microsoft Excel. There were no significant statistical differences between the before and after values of the variables measured in our study. In our study the paired T-test determined that there were no statistical significant differences between the liver function after Esmya administration. Altough there was no evidence of hepatic impairment in the 3 months course of treatment, precautions as the one recomended by EMA, should be respected. Still, more studies are needed in order to rule out the potential harmful effect of UPA on the liver, taking into account detailed liver function evaluation and extended laboratory tests. Until then, the temporary safety measures issued by the European Medicines Agency, are to be respected. The measures include: no use of UPA for women with known liver conditions, careful monitoring of liver function monthly for the patients under treatment and at four weeks after, and immediate discontinuation and report of any adverse complaints.
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48

Kaixin, Zhang, Gu Xuedie, Lan Jing, Zhang Yiming, Pervez Ahmed Khoso, Liu Zhaoyi, and Li Shu. "Selenium-deficient diet induces inflammatory response in the pig adrenal glands by activating TLR4/NF-κB pathway via miR-30d-R_1." Metallomics 13, no. 7 (June 16, 2021). http://dx.doi.org/10.1093/mtomcs/mfab037.

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Abstract Selenium (Se) is an important trace element to maintain the body's dynamic balance. Lack of Se can cause inflammation. Studies have shown that inflammation often leads to disorders of the hypothalamic–pituitary–adrenal axis, but the mechanism by which Se deficiency causes inflammation of the porcine adrenal glands is still unclear. In order to study the effect of Se deficiency on the adrenal glands of pigs, we obtained Se-deficient pig adrenal glands through a low-Se diet. The results of mass spectrometry showed that the Se content in the Se-deficient group was only one-tenth of the control group. We detected the expression of the toll-like receptor 4 (TLR4) and downstream factors by qRT-PCR and Western blotting, and found that the lack of Se affected the TLR4/NF-κB pathway. It is known that miR-155-3p, miR-30d-R_1, and miR-146b have all been verified for targeting relationship with TLR4. We confirmed by qRT-PCR that miR-30d-R_1 decreased most significantly in the Se-deficient pig model. Then we tested 25 selenoproteins and some indicators of oxidative stress. It is confirmed that Se deficiency reduces the antioxidant capacity and induces oxidative stress in pig adrenal tissue. In short, a diet lacking Se induces oxidative stress in pig adrenal tissues and leads to inflammation through the miR-30d-R_1/TLR4 pathway. This study provides a reference for the prevention of adrenal inflammation in pigs from a nutritional point of view.
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