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1
Cato, A. C., and H. Ponta. "Different regions of the estrogen receptor are required for synergistic action with the glucocorticoid and progesterone receptors." Molecular and Cellular Biology 9, no. 12 (December 1989): 5324–30. http://dx.doi.org/10.1128/mcb.9.12.5324.
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Estrogen and progesterone or estrogen and glucocorticoid receptors functionally cooperate in gene activation if their cognate binding sites are close to one another. These interactions have been described as synergism of action of the steroid receptors. The mechanism by which synergism is achieved is not clear, although protein-protein interaction of the receptors is one of the favorite models. In transfection experiments with receptor expression vectors and a reporter gene containing estrogen and progesterone-glucocorticoid receptor binding sites, we have examined the effects that different portions of the various receptors have on synergism. N-terminal domains of the chicken progesterone and human glucocorticoid receptors, when deleted, abolished the synergistic action of these receptors with the estrogen receptor. Deletion of the carboxy-terminal amino acids 341 to 595 of the estrogen receptor produced a mutant receptor that could not trans-activate on its own. This mutant receptor did not affect the action of the glucocorticoid receptor but functioned synergistically with the progesterone receptor. We therefore conclude that the synergistic action of the receptors for estrogen and progesterone is mechanistically different from the synergistic action of the receptors for estrogen and glucocorticoid.
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Cato, A. C., and H. Ponta. "Different regions of the estrogen receptor are required for synergistic action with the glucocorticoid and progesterone receptors." Molecular and Cellular Biology 9, no. 12 (December 1989): 5324–30. http://dx.doi.org/10.1128/mcb.9.12.5324-5330.1989.
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Estrogen and progesterone or estrogen and glucocorticoid receptors functionally cooperate in gene activation if their cognate binding sites are close to one another. These interactions have been described as synergism of action of the steroid receptors. The mechanism by which synergism is achieved is not clear, although protein-protein interaction of the receptors is one of the favorite models. In transfection experiments with receptor expression vectors and a reporter gene containing estrogen and progesterone-glucocorticoid receptor binding sites, we have examined the effects that different portions of the various receptors have on synergism. N-terminal domains of the chicken progesterone and human glucocorticoid receptors, when deleted, abolished the synergistic action of these receptors with the estrogen receptor. Deletion of the carboxy-terminal amino acids 341 to 595 of the estrogen receptor produced a mutant receptor that could not trans-activate on its own. This mutant receptor did not affect the action of the glucocorticoid receptor but functioned synergistically with the progesterone receptor. We therefore conclude that the synergistic action of the receptors for estrogen and progesterone is mechanistically different from the synergistic action of the receptors for estrogen and glucocorticoid.
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Johannessen, Molly, Dominique Fontanilla, Timur Mavlyutov, Arnold E. Ruoho, and Meyer B. Jackson. "Antagonist action of progesterone at σ-receptors in the modulation of voltage-gated sodium channels." American Journal of Physiology-Cell Physiology 300, no. 2 (February 2011): C328—C337. http://dx.doi.org/10.1152/ajpcell.00383.2010.
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σ-Receptors are integral membrane proteins that have been implicated in a number of biological functions, many of which involve the modulation of ion channels. A wide range of synthetic ligands activate σ-receptors, but endogenous σ-receptor ligands have proven elusive. One endogenous ligand, dimethyltryptamine (DMT), has been shown to act as a σ-receptor agonist. Progesterone and other steroids bind σ-receptors, but the functional consequences of these interactions are unclear. Here we investigated progesterone binding to σ1- and σ2-receptors and evaluated its effect on σ-receptor-mediated modulation of voltage-gated Na+ channels. Progesterone binds both σ-receptor subtypes in liver membranes with comparable affinities and blocks photolabeling of both subtypes in human embryonic kidney 293 cells that stably express the human cardiac Na+ channel Nav1.5. Patch-clamp recording in this cell line tested Na+ current modulation by the σ-receptor ligands ditolylguanidine, PB28, (+)SKF10047, and DMT. Progesterone inhibited the action of these ligands to varying degrees, and some of these actions were reduced by σ1-receptor knockdown with small interfering RNA. Progesterone inhibition of channel modulation by drugs was consistent with stronger antagonism of σ2-receptors. By contrast, progesterone inhibition of channel modulation by DMT was consistent with stronger antagonism of σ1-receptors. Progesterone binding to σ-receptors blocks σ-receptor-mediated modulation of a voltage-gated ion channel, and this novel membrane action of progesterone may be relevant to changes in brain and cardiovascular function during endocrine transitions.
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Grunberg, Steven M., Anna Marie Daniels, Helmut Muensch, John R. Daniels, Leslie Bernstein, Virginia Kortes, and Martin H. Weiss. "Correlation of meningioma hormone receptor status with hormone sensitivity in a tumor stem-cell assay." Journal of Neurosurgery 66, no. 3 (March 1987): 405–8. http://dx.doi.org/10.3171/jns.1987.66.3.0405.
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✓ Several investigators have detected progesterone receptors in a high percentage of meningioma specimens and have noted progesterone receptors to be more common than estrogen receptors in these specimens. However, a functional significance of such hormone receptor positivity in control of meningioma growth has not been described. This paper describes a paired test of the estrogen and progesterone receptor assay as the biochemical assay and of the human tumor stem-cell clonogenic assay (HTSCCA) as the functional assay in 17 meningioma specimens. Only one (6%) of the 17 specimens was estrogen receptor-positive, while 11 (69%) of 16 specimens were progesterone receptor-positive. The HTSCCA revealed that only two (15%) of 13 specimens were sensitive to estradiol while five (31%) of 16 specimens were sensitive to progesterone. Comparison of progesterone results for the 15 specimens on which both hormone receptor assay and HTSCCA were performed revealed correlation in a majority of cases; four specimens were positive for both assays and five specimens were negative for both assays. No specimen that was negative for progesterone receptors was sensitive to progesterone by HTSCCA. These results suggest that the hormone receptor and sensitivity pattern of meningiomas may differ from that of breast cancer, and that progesterone addition or ablation may be a reasonable therapeutic approach for meningiomas.
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Mangal, Suruchi, Manisha Sharma, Mridu Manjari, Rahul Mannan, and Sunit Tandon. "Expression Of Androgen Receptor, Estrogen Receptor And Progesterone Receptor In Endometrial Carcinoma (Immunohistochemical Study)." Annals of Pathology and Laboratory Medicine 7, no. 5 (May 28, 2020): A248–252. http://dx.doi.org/10.21276/apalm.2726.
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Berg, Nicholas J., Douglas S. Colvard, H. Bryan Neel, Louis H. Weiland, and Thomas C. Spelsberg. "Progesterone Receptors in Carcinomas of the Upper Aerodigestive Tract." Otolaryngology–Head and Neck Surgery 101, no. 5 (November 1989): 527–36. http://dx.doi.org/10.1177/019459988910100503.
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This study had three major goals: (1) to vigorously verify the presence of progesterone receptors in squamous cell carcinoma of the upper aerodigestive tract (HN-SCC). Antiprogesterone receptor monoclonal antibodies revealed a distinct band at approximately 120 kilodaltons in samples taken from two of four patients with HN-SCC. These results illustrate that progesterone receptor in HN-SCC has the same molecular weight as progesterone receptor in normal human uterus and human breast cancer. Steroid specificity and saturability results support the evidence that it is true progesterone receptors that are measured and not other receptors or sex steroid-binding globulins; (2) to confirm the biochemical function of progesterone receptors in HN-SCC by assessing the binding of progesterone receptor to acceptor sites on chromosomes in the nucleus; and (3) to establish the clinical significance of progesterone receptor measurement. Patients with positive assays were more likely to be free of disease a mean of 6 months after resection. We used logistic regression to account for site of primary disease, grade of tumor, and stage of disease. This logistic regression was significant with a p = 0.014. Patients with a binding index greater than 2 (19 of 73 patients) were 4.34 times more likely to be free of disease than patients with negative assays.
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Wathes, D. C., G. E. Mann, J. H. Payne, P. R. Riley, K. R. Stevenson, and G. E. Lamming. "Regulation of oxytocin, oestradiol and progesterone receptor concentrations in different uterine regions by oestradiol, progesterone and oxytocin in ovariectomized ewes." Journal of Endocrinology 151, no. 3 (December 1996): 375–93. http://dx.doi.org/10.1677/joe.0.1510375.
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Abstract The regulation of oxytocin, oestradiol and progesterone receptors in different uterine cell types was studied in ovariectomized ewes. Animals were pretreated with a progestogen sponge for 10 days followed by 2 days of high-dose oestradiol to simulate oestrus. They then received either low-dose oestradiol (Group E), low-dose oestradiol plus progesterone (Group P) or low-dose oestradiol, progesterone and oxytocin (via osmotic minipump; Group OT). Animals (three to six per time-point) were killed following ovariectomy (Group OVX), at oestrus (Group O) or following 8, 10, 12 or 14 days of E, P or OT treatment. In a final group, oxytocin was withdrawn on day 12 and ewes were killed on day 14 (Group OTW). Oxytocin receptor concentrations and localization in the endometrium and myometrium were measured by radioreceptor assay, in situ hybridization and autoradiography with the iodinated oxytocin receptor antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH29]-vasotocin. Oestradiol and progesterone receptors were localized by immunocytochemistry. Oxytocin receptors were present in the luminal epithelium and superficial glands of ovariectomized ewes. In Group O, endometrial oxytocin receptor concentrations were high (1346 ± 379 fmol [3H]oxytocin bound mg protein−1) and receptors were also located in the deep glands and caruncular stroma in a pattern resembling that found at natural oestrus. Continuing low-dose oestradiol was unable to sustain high endometrial oxytocin receptor concentrations with values decreasing significantly to 140 ± 20 fmol mg protein−1 (P<0·01), localized to the luminal epithelium and caruncular stroma but not the glands. Progesterone treatment initially abolished all oxytocin receptors with none present on days 8 or 10. They reappeared in the luminal epithelium only between days 12 and 14 to give an overall concentration of 306 ± 50 fmol mg protein−1. Oxytocin treatment caused a small increase in oxytocin receptor concentration in the luminal epithelium on days 8 and 10 (20 ± 4 in Group P and 107 ± 35 fmol mg protein−1 in Group OT, P<0·01) but the rise on day 14 was not affected (267 ± 82 in Group OT and 411 ± 120 fmol mg protein−1 in Group OTW). In contrast, oestradiol treatment was able to sustain myometrial oxytocin receptors (635 ± 277 fmol mg protein−1 in Group O and 255 ± 36 in Group E) and there was no increase over time in Groups P, OT and OTW with values of 61 ± 18, 88 ± 53 and 114 ± 76 fmol mg protein−1 respectively (combined values for days 8–14). Oestradiol receptor concentrations were high in all uterine regions in Group O. This pattern and concentration was maintained in Group E. In all progesterone-treated ewes, oestradiol receptor concentrations were lower in all regions at all time-points. The only time-related change occurred in the luminal epithelium in which oestradiol receptors were undetectable on day 8 but developed by day 10 of progesterone treatment. Progesterone receptors were present at moderate concentrations in the deep glands, caruncular stroma, deep stroma and myometrium in Group O. Oestradiol increased progesterone receptors in the luminal epithelium, superficial glands, deep stroma and myometrium. Progesterone caused the loss of its own receptor from the luminal epithelium and superficial glands and decreased its receptor concentration in the deep stroma and myometrium at all time-points. There was a time-related loss of progesterone receptors from the deep glands of progesterone-treated ewes between days 8 and 14. These results show differences in the regulation of receptors between uterine regions. In particular, loss of the negative inhibition by progesterone on the oxytocin receptor by day 14 occurred only in the luminal epithelium, but is unlikely to be a direct effect of progesterone as no progesterone receptors were present on luminal epithelial cells between days 8 and 14. The presence of oxytocin receptors in the luminal epithelium of ovariectomized ewes suggests that oestradiol is not essential for oxytocin receptor synthesis at this site. Oestradiol was able to sustain its own receptor at all sites, but high circulating progesterone was always inhibitory to oestradiol receptors. In general, oestradiol stimulated progesterone receptors in epithelial cells whereas progesterone abolished its own receptor from epithelial cells over a period of time, but had a lesser effect on stromal cells. The concentration of all three receptors is therefore differentially regulated between different uterine cell types, suggesting the importance of paracrine effects which remain to be elucidated. Journal of Endocrinology (1996) 151, 375–393
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Bracali, G., A. M. Caracino, F. Rossodivita, C. Bianchi, M. G. Loli, and M. Bracali. "Estrogen and Progesterone Receptors in Human Colorectal Tumour Cells (Study of 70 Cases)." International Journal of Biological Markers 3, no. 1 (January 1988): 41–48. http://dx.doi.org/10.1177/172460088800300108.
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Estrogen and progesterone receptors were studied in 70 cases of human colorectal cancer by a cytochemical technique. 28.5% of the cases were estrogen-receptor positive and 42.8% progesterone-receptor positive. There was no difference between the sexes for estrogen receptors but the women had more tumours with progesterone receptors than men. The presence of receptors is unrelated to the differentiation of the tumour. More colon tumours were positive than those of the sigma and rectum. The concentration of cells with receptors in positive cancer cases tended to be low or medium-low.
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Nidoieva, Z. M., and A. P. Latsyshyna. "Effect of progesterone on the MGMT gene expression in MCF7, HEp-2 and 293 cells." Visnik ukrains'kogo tovaristva genetikiv i selekcioneriv 18, no. 1-2 (January 29, 2021): 16–21. http://dx.doi.org/10.7124/visnyk.utgis.18.1-2.1350.
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Aims: to investigate the steroid hormone progesterone effect on the human MGMT gene expression at the mRNA and protein levels in cell lines with different expression patterns of the nuclear progesterone receptors and membrane receptor PGRMC1. Methods: cell culture, RNA / protein isolation, cDNA synthesis, real-time polymerase chain reaction, Western blot analysis. Results: We observe the MGMT gene upregulation by progesterone at both mRNA and protein levels. Conclusions the effect of progesterone on MGMT expression is more complex than direct regulation through the classical nuclear receptor.Keywords: O6-methylguanine-DNA methyltransferase (MGMT), progesterone, nuclear progesterone receptors (nPR), progesterone receptor membrane component 1 (PGRMC1), gene expression regulation.
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Brocklehurst, D., C. E. Wilde, J. A. Finbow, R. Brett, A. E. Champion, and D. G. Dewhurst. "Relative importance of estrogen and progesterone receptor assays as prognostic indicators in primary breast cancer: a short-term study." Clinical Chemistry 35, no. 2 (February 1, 1989): 238–40. http://dx.doi.org/10.1093/clinchem/35.2.238.
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Abstract This short-term study of the relative importance of estrogen and progesterone receptors shows that progesterone receptor correlates better than estrogen receptor with tumor recurrence regardless of lymph-node status. Life-table analysis has effectively identified only two groups of patients that may be classified by progesterone receptor status alone. Progesterone-receptor negativity correlated well with tumors of histological Grade III; estrogen-receptor positivity correlated with Grade I and II tumors. The earlier recurrence of Grade III breast tumors may explain why progesterone receptor is a better prognostic indicator than estrogen receptor in short-term studies.
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Baker, ME. "Recent insights into the origins of adrenal and sex steroid receptors." Journal of Molecular Endocrinology 28, no. 3 (June 1, 2002): 149–52. http://dx.doi.org/10.1677/jme.0.0280149.
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The recent cloning by Thornton (2001) of estrogen, progesterone and corticoid receptors from lamprey provides important insights into the early evolution of adrenal and sex steroid receptors and an opportunity to elucidate the ancient steroids that regulated gene transcription. Inclusion of lamprey sequences in a steroid receptor phylogeny indicates that the estrogen receptor is the most ancient of these receptors, followed by the progesterone receptor and the corticoid receptor. Thornton proposed that estradiol was the earliest of the steroids to activate a steroid receptor. An alternative hypothesis is that a steroid in the Delta(5) pathway activated the ancestral estrogen receptor.
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Wathes, D. C., and M. Hamon. "Localization of oestradiol, progesterone and oxytocin receptors in the uterus during the oestrous cycle and early pregnancy of the ewe." Journal of Endocrinology 138, no. 3 (September 1993): 479—NP. http://dx.doi.org/10.1677/joe.0.1380479.
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ABSTRACT Uterine tissue samples were collected from 47 ewes at various stages of the oestrous cycle and early pregnancy (until day 21) and during seasonal anoestrus. Cryostat sections were immunostained to determine the localization of oestradiol and progesterone receptors using specific monoclonal antibodies. Oxytocin receptors were localized by autoradiography in sections from the same ewes using the 125I-labelled oxytocin antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH29]- vasotocin. Plasma progesterone measurements were made during the preceding cycle up to the time of slaughter. Oestradiol receptor concentrations were maximal in all regions of the tract at oestrus. Immunostaining of the luminal epithelium, superficial glandular epithelium, stroma and myometrium decreased in the early luteal phase but was maintained for longer in the deep glands. Progesterone receptor immunostaining in the luminal epithelium and superficial glands developed in the early luteal phase (days 1–2) with a somewhat later appearance in the deep glands (days 5–7). Progesterone receptor concentrations in the stroma and myometrium also reached a maximum in the early luteal phase. Myometrial staining was clearly maintained throughout the luteal phase whereas stromal staining was variable between ewes. For both oestradiol and progesterone receptors no differences were apparent between pregnant and non-pregnant ewes between days 2 and 12, but pregnant ewes did not show the general increases in oestradiol receptor staining associated with luteolysis on days 14–15. Oxytocin receptors first developed in the luminal epithelium of non-pregnant ewes on day 14 of the cycle and spread to the superficial glands, caruncular stroma, deep glands and myometrium at oestrus before decreasing in reverse order on days 1–2. Specific binding was not detectable on days 5–12 of the cycle or on days 14 or 21 of pregnancy. The appearance of oxytocin receptors in the luminal epithelium on day 14 preceded that of both the oestradiol and progesterone receptors in the epithelial cells and the fall in plasma progesterone. It was followed by the development of oestradiol and oxytocin receptors in the superficial glands, deep glands, caruncular stroma and myometrium, with the two receptor populations showing a significant positive association in these tissues. The loss of oxytocin receptors in all regions occurred as plasma progesterone levels were increasing, but the association between these two variables was only significant in the superficial glands. The development of progesterone receptors in different tissues could not be explained on the basis of either oestradiol receptor content or plasma progesterone. We conclude that all three receptor populations change in a dynamic manner during the oestrous cycle with variations both between days and between different uterine compartments. The complex pattern of receptor formation and loss suggests that, in addition to the circulating steroid hormone concentrations, local paracrine factors are likely to be involved in their regulation. Journal of Endocrinology (1993) 138, 479–491
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Miller, H. M., W. T. Dixon, G. R. Foxcroft, and F. X. Aherne. "Changes in the gene expression of progesterone receptor and prolactin receptor in sow mammary gland between late gestation and lactation." Proceedings of the British Society of Animal Science 1998 (1998): 179. http://dx.doi.org/10.1017/s0308229600033924.
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Lactogenesis is triggered by a rapid decline in plasma progesterone concentration combined with a peak in plasma prolactin concentration; in mice, there is a concurrent loss of mammary progesterone receptors (Haslam and Shyamala, 1980). The aims of this experiment were to determine the pattern of change of progesterone receptor and prolactin receptor mRNA during late gestation and early lactation and to determine whether abundance of mRNA for the two receptors are related to each other, to plasma concentrations of progesterone and prolactin or to piglet performance.
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Miller, H. M., W. T. Dixon, G. R. Foxcroft, and F. X. Aherne. "Changes in the gene expression of progesterone receptor and prolactin receptor in sow mammary gland between late gestation and lactation." Proceedings of the British Society of Animal Science 1998 (1998): 179. http://dx.doi.org/10.1017/s1752756200598317.
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Lactogenesis is triggered by a rapid decline in plasma progesterone concentration combined with a peak in plasma prolactin concentration; in mice, there is a concurrent loss of mammary progesterone receptors (Haslam and Shyamala, 1980). The aims of this experiment were to determine the pattern of change of progesterone receptor and prolactin receptor mRNA during late gestation and early lactation and to determine whether abundance of mRNA for the two receptors are related to each other, to plasma concentrations of progesterone and prolactin or to piglet performance.
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VERRIJDT, Guy, Annemie HAELENS, Erik SCHOENMAKERS, Wilfried ROMBAUTS, and Frank CLAESSENS. "Comparative analysis of the influence of the high-mobility group box 1 protein on DNA binding and transcriptional activation by the androgen, glucocorticoid, progesterone and mineralocorticoid receptors." Biochemical Journal 361, no. 1 (December 17, 2001): 97–103. http://dx.doi.org/10.1042/bj3610097.
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We performed a comparative analysis of the effect of high-mobility group box protein 1 (HMGB1) on DNA binding by the DNA-binding domains (DBDs) of the androgen, glucocorticoid, progesterone and mineralocorticoid receptors. The affinity of the DBDs of the different receptors for the tyrosine aminotransferase glucocorticoid response element, a classical high-affinity binding element, was augmented up to 7-fold by HMGB1. We found no major differences in the effects of HMGB1 on DNA binding between the different steroid hormone receptors. In transient transfection assays, however, HMGB1 significantly enhances the activity of the glucocorticoid and progesterone receptors but not the androgen or mineralocorticoid receptor. We also investigated the effect of HMGB1 on the binding of the androgen receptor DBD to a subclass of directly repeated response elements that is recognized exclusively by the androgen receptor and not by the glucocorticoid, progesterone or mineralocorticoid receptor. Surprisingly, a deletion of 26 amino acid residues from the C-terminal extension of the androgen receptor DBD does not influence DNA binding but destroys its sensitivity to HMGB1. Deletion of the corresponding fragment in the DBDs of the glucocorticoid, progesterone and mineralocorticoid receptor destroyed their DNA binding. This 26-residue fragment is therefore essential for the influence of HMGB1 on DNA recognition by all steroid hormone receptors that were tested. However, it is dispensable for DNA binding by the androgen receptor.
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Meikle, A., C. Tasende, C. Sosa, and E. G. Garófalo. "The role of sex steroid receptors in sheep female reproductive physiology." Reproduction, Fertility and Development 16, no. 4 (2004): 385. http://dx.doi.org/10.1071/rd04036.
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Cell responsiveness to steroid hormones is related to the number and affinity of its receptors, thus factors affecting steroid expression will influence tissue sensitivity and functionality. The present review discusses the role of oestrogen and progesterone receptors in sheep female reproductive physiology. The mechanism of steroid hormone action in the target cell is introduced first; the tissue distribution, physiological functions and regulation of oestrogen receptor subtypes and progesterone receptor isoforms in ruminants are reported. The role of steroid receptors in target tissues (with emphasis on the uterus and pituitary gland) during different physiological events is addressed in an attempt to clarify oestrogen and progesterone actions in different developmental and reproductive stages: prepubertal period, oestrous cycle, pregnancy, post-partum period and seasonal anoestrus. The present review shows how the distinct reproductive stages are accompanied by dramatic changes in uterine receptor expression. The role of oestrogen and progesterone receptors in the molecular mechanism responsible for premature luteolysis that results in subnormal luteal function is discussed. Finally, the effect of nutrition on sex steroid receptor expression and the involvement on reproductive performance is reported.
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J, Prashanthi, and Ramaswamy Naik M. "A study on estrogen receptor, progesterone receptors, HER-2NEU status in breast cancer cases attending to a tertiary care hospital of Andhra Pradesh." Asian Pacific Journal of Health Sciences 2, no. 4S (2015): 67–71. http://dx.doi.org/10.21276/apjhs.2015.2.2s.13.
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Welter, Brenda H., Elizabeth L. Hansen, Karla J. Saner, Yangzhan Wei, and Thomas M. Price. "Membrane-bound Progesterone Receptor Expression in Human Aortic Endothelial Cells." Journal of Histochemistry & Cytochemistry 51, no. 8 (August 2003): 1049–55. http://dx.doi.org/10.1177/002215540305100808.
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Observational studies demonstrate that estradiol and progesterone affect vasoreactivity. In animal studies, progesterone treatment causes immediate relaxation of precontracted arteries with inhibition of calcium influx in vascular endothelial and smooth muscle cells, suggesting a non-genomic mechanism of action. In this study we investigated the presence of novel membrane-bound progesterone receptors in human aortic endothelial cells and correlated the expression with cell-cycle stage. Western blotting analysis with an antibody directed to the hormone-binding domain of the classic progesterone receptors shows predominant bands at 100 and 60 kD, whereas analysis with an antibody to the DNA-binding region shows only the 100-kD band. In contrast, classic nuclear progesterone receptors B and A are identified at 116 and 94 kD in similarly processed T47D cells. Both novel bands localize to the membrane fraction after differential centrifugation. Plasma membrane-bound progesterone receptor was further shown with immunofluorescent antibody and ligand-binding studies in a small percentage of human aortic endothelial cells. Fluorescent activated cell sorting demonstrated that approximately 8% of the human aortic endothelial cells expressed a plasma membrane progesterone receptor and that a greater percentage of the expressing cells were in the G2/M-phase of the cell cycle. Treatment with progesterone conjugated to BSA did not show any significant cell-cycle changes. Plasma membrane-bound progesterone receptor in vascular endothelial cells may regulate the non-genomic actions of progesterone, and expression of the receptor appears to vary with cell cycle stage.
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Nikolaou, Marinos, Dimitra Koumoundourou, Panagiota Ravazoula, Margarita Papadopoulou, Georgios Michail, and Georgios Decavalas. "An immunohistochemical analysis of sex-steroid receptors, tumor suppressor gene p53 and Ki-67 in the normal and neoplastic uterine cervix squamous epithelium." Medical review 67, no. 7-8 (2014): 202–7. http://dx.doi.org/10.2298/mpns1408202n.
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Introduction. Malignant transformation of sex-steroid dependent tissues is associated with the loss of expression of sex steroid receptors as well as of the tumor suppression gene p53. The aim of this study is to evaluate the expression of sex-steroid receptors, p53 and Ki-67 in specimens from pre-malignant and malignant cervical epithelial lesions throughout the menstrual cycle. Material and Methods. Immunohistochemical staining was performed on formalin fixed, paraffin embedded tissue sections of normal squamous cervical epithelium, cervical intraepithelial neoplasia and invasive squamous cervical carcinoma, specimens utilizing antibodies against estrogen receptors, progesterone receptors, p53 protein and Ki-67 antigen. Results. In the samples taken from the normal cervical tissue, basal cells were usually estrogen receptor-positive, progesterone receptornegative, p53-negative and Ki-67-negative throughout the menstrual cycle. In contrast, para-basal cells were estrogen receptorpositive and progesterone receptor-negative in the follicular phase, but estrogen receptor-negative and progesterone receptor -positive and Ki-67 positive in the luteal phase. In cervical precancerous and cancer tissue samples (cervical intraepithelial neoplasia and squamous cervical carcinoma), the expression of estrogen receptors decreased. 31.15% of cervical intraepithelial neoplasia and 11.5% of squamous cervical carcinoma were positive for estrogen receptors. However, the expression of progesterone receptors increased. 29.5% of cervical intraepithelial neoplasia and 49.2% of squamous cervical carcinoma were positive for progesterone receptors. Positive staining for p53 was observed in 15 (24.59%) cases of cervical intraepithelial neoplasia and in 39 (64%) of squamous cervical carcinoma. The expression Ki-67 index in squamous cervical carcinoma cases (47.60%) was significantly higher than of cervical intraepithelial neoplasia cases (30.2%) (p=0.041). Conclusion. The findings of this study suggest that tumor cervical cells evade normal growth control by sex steroid hormones while synchronously abnormal regulatory mechanisms acquire control of the cell cycle.
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Schrell, Uwe M. H., Eric F. Adams, Rudolf Fahlbusch, Robert Greb, Gustav Jirikowski, Reinhard Prior, and Flavio J. Ramalho-Ortigao. "Hormonal dependency of cerebral meningiomas." Journal of Neurosurgery 73, no. 5 (November 1990): 743–49. http://dx.doi.org/10.3171/jns.1990.73.5.0743.
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✓ Female sex steroid receptors were examined in 50 human cerebral meningiomas. For estrogen receptors, high-affinity binding sites (dissociation constant (Kd): 0.05 to 0.2 nM) were found in the cytosolic fraction with a capacity of less than 4 fmol/mg protein in 10 meningiomas using a dextran-coated charcoal (DCC) assay. In the same cytosolic fraction, the solid-phase enzyme immunoassay revealed only one cytosol with a positive colorimetric reaction equal to 5 fmol/mg protein. However, in the nuclear compartment, none of the tumors stained positively for estrogen receptors with immunohistochemical techniques. In addition, the most convincing evidence for the absence of estrogen receptors was obtained by in situ hybridization using an oligonucleotide probe complementary to a fraction of the human receptor messenger ribonucleic acid (mRNA). In none of the 50 meningiomas was the expression of estrogen mRNA coding for the estrogen receptor detected. For progesterone receptors, high-affinity binding sites (Kd: 0.3 to 2.6 nM) were found in 49 of the 50 tumors using a DCC assay. In the same cytosols, solid-phase enzyme immunoassay revealed that each tumor was positive for progesterone receptors. However, in the nuclear compartment, only five tumors had partially positive staining for progesterone receptors with immunohistochemical techniques. Within the confines of this study, it is concluded that: 1) the estrogen receptor is generally absent in meningioma tissue, and 2) the progesterone receptor is mainly absent in the nuclear compartment, leading to the conclusion that the cytosolic progesterone receptor may be an inactive form. This study suggests that female sex steroid receptors are not primarily involved in the proliferative rate of cerebral meningiomas and that they are of no current significance as markers for adjuvant medical therapy of most meningiomas.
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Maxwell, Marius, Theofanis Galanopoulos, Janine Neville-Golden, and Harry N. Antoniades. "Expression of androgen and progesterone receptors in primary human meningiomas." Journal of Neurosurgery 78, no. 3 (March 1993): 456–62. http://dx.doi.org/10.3171/jns.1993.78.3.0456.
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✓ Meningiomas are common brain tumors that show a predilection for females and become more aggressive during pregnancy and menses. The existence of gender-specific hormone receptors in meningiomas has long been a matter of controversy; the recent cloning of androgen, estrogen, and progesterone receptors has facilitated their direct evaluation. The authors have demonstrated the expression of androgen and progesterone receptor messenger ribonucleic acid and protein product in nine primary human meningiomas by Northern blot analysis. Cellular localization was achieved by in situ hybridization analysis. Estrogen receptor expression was not detected. Normal adult meninges were shown to express very low levels of both androgen and progesterone receptors.
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Moussatche, Patricia, and Thomas J. Lyons. "Non-genomic progesterone signalling and its non-canonical receptor." Biochemical Society Transactions 40, no. 1 (January 19, 2012): 200–204. http://dx.doi.org/10.1042/bst20110638.
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The steroid hormone progesterone regulates many critical aspects of vertebrate physiology. The nuclear receptor for progesterone functions as a ligand-activated transcription factor, directly regulating gene expression. This type of signalling is referred to as the ‘genomic’ pathway. Nevertheless, progesterone also stimulates rapid physiological effects that are independent of transcription. This pathway, termed ‘non-genomic’, is mediated by the mPRs (membrane progesterone receptors). These mPRs belong to a larger class of membrane receptors called PAQRs (progestin and adipoQ receptors), which include receptors for adiponectin in vertebrates and osmotin in fungi. mPRs have been shown to activate inhibitory G-proteins, suggesting that they act as GPCRs (G-protein-coupled receptors). However, PAQRs do not resemble GPCRs with respect to topology or conserved sequence motifs. Instead, they more closely resemble proteins in the alkaline ceramidase family and they may possess enzymatic activity. In the present paper, we highlight the evidence in support of each model and what is currently known for PAQR signal transduction of this non-canonical receptor.
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Gion, Massimo, Riccardo Mione, Ruggero Dittadi, Luciano Griggio, Gabriele Munegato, Marco Valescchi, Orfeo Del Maschio, Stefano Fasan, and Giuliano Bruscagnin. "Estrogen and Progesterone Receptors in Breast Carcinoma and in Nonmalignant Breast Tissue." Tumori Journal 71, no. 5 (October 1985): 477–81. http://dx.doi.org/10.1177/030089168507100511.
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Since 1983 we have studied the relationship, in the same patient, between receptor status in breast carcinoma and in nonmalignant breast tissue. Fifty patients have been evaluated to date. The total unoccupied cytosol estrogen and progesterone receptors were determined by a dextran-coated charcoal method. In nonmalignant breast tissue we found a measurable receptor concentration above the sensitivity of the method in 62 % of cases for estrogen receptors and in 44 % of cases for progesterone receptors. No relationships were found between the receptor level of each tumor and that of the corresponding benign tissue. The data suggest that the levels of the receptors in the tumor and in the nonmalignant tissue are totally independent.
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Bonthuis, Paul J., James K. Patteson, and Emilie F. Rissman. "Acquisition of Sexual Receptivity: Roles of Chromatin Acetylation, Estrogen Receptor-α, and Ovarian Hormones." Endocrinology 152, no. 8 (June 7, 2011): 3172–81. http://dx.doi.org/10.1210/en.2010-1001.
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Sexually naïve, hormone-primed, C57BL/6J female mice are not receptive to mating attempts by conspecific males. Repeated experience with sexually active males and concurrent treatment with estradiol and progesterone gradually increases female receptivity over the course of five trials to maximal levels. Ovarian hormones activate their cognate nuclear steroid receptors estrogen receptor-α and progesterone receptor to induce female sexual receptivity. Nuclear receptors recruit coactivators of transcription that include histone acetyltransferases to hormone responsive genes. In this set of studies, we found that the histone deacetylase inhibitor sodium butyrate enhances the experiential acquisition of receptivity. Evidence is provided that the actions of sodium butyrate on receptivity require activated estrogen receptor-α and progesterone.
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Guennoun, Rachida. "Progesterone in the Brain: Hormone, Neurosteroid and Neuroprotectant." International Journal of Molecular Sciences 21, no. 15 (July 24, 2020): 5271. http://dx.doi.org/10.3390/ijms21155271.
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Progesterone has a broad spectrum of actions in the brain. Among these, the neuroprotective effects are well documented. Progesterone neural effects are mediated by multiple signaling pathways involving binding to specific receptors (intracellular progesterone receptors (PR); membrane-associated progesterone receptor membrane component 1 (PGRMC1); and membrane progesterone receptors (mPRs)) and local bioconversion to 3α,5α-tetrahydroprogesterone (3α,5α-THPROG), which modulates GABAA receptors. This brief review aims to give an overview of the synthesis, metabolism, neuroprotective effects, and mechanism of action of progesterone in the rodent and human brain. First, we succinctly describe the biosynthetic pathways and the expression of enzymes and receptors of progesterone; as well as the changes observed after brain injuries and in neurological diseases. Then, we summarize current data on the differential fluctuations in brain levels of progesterone and its neuroactive metabolites according to sex, age, and neuropathological conditions. The third part is devoted to the neuroprotective effects of progesterone and 3α,5α-THPROG in different experimental models, with a focus on traumatic brain injury and stroke. Finally, we highlight the key role of the classical progesterone receptors (PR) in mediating the neuroprotective effects of progesterone after stroke.
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Hlavaty, Juraj, Reinhard Ertl, Ingrid Miller, and Cordula Gabriel. "Expression of Progesterone Receptor Membrane Component 1 (PGRMC1), Progestin and AdipoQ Receptor 7 (PAQPR7), and Plasminogen Activator Inhibitor 1 RNA-Binding Protein (PAIRBP1) in Glioma SpheroidsIn Vitro." BioMed Research International 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/8065830.
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Objective.Some effects of progesterone on glioma cells can be explained through the slow, genomic mediated responsevianuclear receptors; the other effects suggest potential role of a fast, nongenomic action mediated by membrane-associated progesterone receptors.Methods.The effects of progesterone treatment on the expression levels of progesterone receptor membrane component 1 (PGRMC1), plasminogen activator inhibitor 1 RNA-binding protein (PAIRBP1), and progestin and adipoQ receptor 7 (PAQR7) on both mRNA and protein levels were investigated in spheroids derived from human glioma cell lines U-87 MG and LN-229.Results.The only significant alteration at the transcript level was the decrease in PGRMC1 mRNA observed in LN-229 spheroids treated with 30 ng/mL of progesterone. No visible alterations at the protein levels were observed using immunohistochemical analysis. Stimulation of U-87 MG spheroids resulted in an increase of PGRMC1 but a decrease of PAIRBP1 protein. Double immunofluorescent detection of PGRMC1 and PAIRBP1 identified the two proteins to be partially colocalized in the cells. Western blot analysis revealed the expected bands for PGRMC1 and PAIRBP1, whereas two bands were detected for PAQR7.Conclusion.The progesterone action is supposed to be mediatedviamembrane-associated progesterone receptors as the nuclear progesterone receptor was absent in tested spheroids.
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Xu, Wenming, Ke Wang, Yan Chen, Xiao Tong Liang, Mei Kuen Yu, Huanxun Yue, and M. Louise Tierney. "Sperm gamma-aminobutyric acid type A receptor delta subunit (GABRD) and its interaction with purinergic P2X2 receptors in progesterone-induced acrosome reaction and male fertility." Reproduction, Fertility and Development 29, no. 10 (2017): 2060. http://dx.doi.org/10.1071/rd16294.
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The mechanism underlying the non-genomic action of progesterone in sperm functions and related Ca2+ mobilisation remains elusive. Herein we report the expression of gamma-aminobutyric acid type A receptor delta subunit (GABRD) in human and rodent sperm and its involvement in mediating the progesterone-induced acrosome reaction. GABRD was localised in the sperm head/neck region. A δ(392–422)-specific inhibitory peptide against GABRD blocked the progesterone-induced acrosome reaction and the associated increase in intracellular Ca2+. Similarly, an inhibitory effect against both progesterone-induced Ca2+ influx and the acrosome reaction was observed with a P2X2 receptor antagonist. The lack of synergism between the GABRD and P2X2 inhibitors suggests that these two receptors are playing a role in the same pathway. Furthermore, a co-immunoprecipitation experiment demonstrated that GABRD could undergo protein–protein interactions with the Ca2+-conducting P2X2 receptor. This interaction between the receptors could be reduced following progesterone (10 μM) inducement. Significantly reduced GABRD expression was observed in spermatozoa from infertile patients with reduced acrosome reaction capacity, suggesting that normal expression of GABRD is critical for the sperm acrosome reaction and thus male fertility. The results of the present study indicate that GABRD represents a novel progesterone receptor or modulator in spermatozoa that is responsible for the progesterone-induced Ca2+ influx required for the acrosome reaction through its interaction with the P2X2 receptor.
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Lin, C. L., and H. L. Buttle. "Progesterone receptor in the mammary tissue of pregnant and lactating gilts and the effect of tamoxifen treatment during late gestation." Journal of Endocrinology 130, no. 2 (August 1991): 251–57. http://dx.doi.org/10.1677/joe.0.1300251.
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ABSTRACT An isotope exchange assay using [3H]progesterone was used to examine progesterone receptor moieties in cytosolic extracts obtained from mammary tissue of gilts over the course of pregnancy and lactation, and during treatment of pregnant gilts with tamoxifen. Scatchard analysis was used to determine the concentrations and dissociation constants of progesterone receptors. The concentration of progesterone receptor was high at the onset of pregnancy (1394 fmol/mg DNA), fell to a nadir at 45 days (36 fmol/mg DNA), increased to a second maximum at 75 days (1232 fmol/mg DNA) and declined thereafter till parturition: the dissociation constant (Kd) of progesterone for its receptor remained stable during pregnancy with a mean Kd of 0·78 nmol/l. Progesterone receptors were not identifiable at day 21 of lactation. Treatment of pregnant gilts with tamoxifen (100 mg or 1·0 g/gilt per day orally ≡ 0·70 or 7·0 mg/kg per day) did not affect the development of mammary structures or the ability to lactate at parturition; however, mammary progesterone receptor content in tamoxifen-treated animals tended to be lower than the controls at day 90 of pregnancy (15·7±1·56 vs 27·0±3·75 fmol/mg protein respectively). The results show that a temporal relationship exists between oestrogen concentrations in the circulation of pregnant gilts with progesterone receptor content in mammary tissue. Journal of Endocrinology (1991) 130, 251–257
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Brodeur, P., M. Mockus, R. McCullough, and L. G. Moore. "Progesterone receptors and ventilatory stimulation by progestin." Journal of Applied Physiology 60, no. 2 (February 1, 1986): 590–95. http://dx.doi.org/10.1152/jappl.1986.60.2.590.
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Progestin is thought to be a ventilatory stimulant but its effectiveness in raising ventilation is variable in humans and other species. We hypothesized that the level of progesterone receptors was an important determinant of the ventilatory response to progestin. Since estradiol induces progesterone receptor formation, we compared the ventilatory effect of the synthetic progestin medroxyprogesterone acetate (MPA) given in combination with estradiol with the effects of estradiol alone, MPA alone, or vehicle (saline) in ovariectomized rats. Animals receiving MPA alone had low numbers of progesterone receptors (2.43 pmol/g uterine wt) and had no change in ventilation, arterial Pco2, or Po2. MPA administration raised ventilation 23 +/- 5%, lowered arterial Pco2 3.2 +/- 0.9 Torr (both P less than 0.01) and tended to raise arterial Po2 when given in combination with estradiol to animals with increased numbers of progesterone receptors (4.85 pmol/g uterine wt). Estradiol alone produced the highest number of progesterone receptors (12.3 pmol/g uterine wt) but had no effect on ventilation or arterial Pco2 and decreased arterial Po2. Combined estradiol plus MPA treatment produced a greater fall in arterial Pco2 than did treatment with MPA alone, estradiol, or saline (all P less than 0.05). These results suggest that both an elevation in progestin levels and progesterone receptor numbers are required to stimulate ventilation.
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Turcotte, B., M. E. Meyer, M. T. Bocquel, L. Bélanger, and P. Chambon. "Repression of the alpha-fetoprotein gene promoter by progesterone and chimeric receptors in the presence of hormones and antihormones." Molecular and Cellular Biology 10, no. 9 (September 1990): 5002–6. http://dx.doi.org/10.1128/mcb.10.9.5002.
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Using transient transfection assays, we showed that repression of the alpha-fetoprotein promoter by intact and deletion mutants of the progesterone receptor and by chimeric progesterone/glucocorticoid-estrogen receptors in the presence of their cognate hormones was closely correlated with their ability to bind to a progesterone/glucocorticoid-responsive element. This negative regulation was also observed in the presence of antihormones, providing evidence that receptor-antihormone complexes can bind to their responsive elements in vivo.
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Turcotte, B., M. E. Meyer, M. T. Bocquel, L. Bélanger, and P. Chambon. "Repression of the alpha-fetoprotein gene promoter by progesterone and chimeric receptors in the presence of hormones and antihormones." Molecular and Cellular Biology 10, no. 9 (September 1990): 5002–6. http://dx.doi.org/10.1128/mcb.10.9.5002-5006.1990.
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Using transient transfection assays, we showed that repression of the alpha-fetoprotein promoter by intact and deletion mutants of the progesterone receptor and by chimeric progesterone/glucocorticoid-estrogen receptors in the presence of their cognate hormones was closely correlated with their ability to bind to a progesterone/glucocorticoid-responsive element. This negative regulation was also observed in the presence of antihormones, providing evidence that receptor-antihormone complexes can bind to their responsive elements in vivo.
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Escobedo, Galileo, Ignacio Camacho-Arroyo, Olivia Tania Hernández-Hernández, Pedro Ostoa-Saloma, Martín García-Varela, and Jorge Morales-Montor. "Progesterone Induces Scolex Evagination of the Human ParasiteTaenia solium: Evolutionary Implications to the Host-Parasite Relationship." Journal of Biomedicine and Biotechnology 2010 (2010): 1–10. http://dx.doi.org/10.1155/2010/591079.
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Taenia soliumcysticercosis is a health problem in underdeveloped and developed countries. Sex hormones are involved in cysticercosis prevalence in female and male pigs. Here, we evaluated the effects of progesterone and its antagonist RU486 on scolex evagination, which is the initial step in the development of the adult worm. Interestingly, progesterone increasedT. soliumscolex evagination and worm growth, in a concentration-independent pattern. Progesterone effects could be mediated by a novelT. soliumprogesterone receptor (TsPR), since RU486 inhibits both scolex evagination and worm development induced by progesterone. Using RT-PCR and western blot, sequences related to progesterone receptor were detected in the parasite. A phylogenetic analysis reveals that TsPR is highly related to fish and amphibian progesterone receptors, whereas it has a distant relation with birds and mammals. Conclusively, progesterone directly acts uponT. soliumcysticerci, possibly through its binding to a progesterone receptor synthesized by the parasite.
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Healy, DL. "Progesterone receptor antagonists and prostaglandins in human fertility regulation: a clinical review." Reproduction, Fertility and Development 2, no. 5 (1990): 477. http://dx.doi.org/10.1071/rd9900477.
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Progesterone receptor antagonists have been developed by substitutions at the 11-beta and 17 side-chain positions of the progestagen norethisterone. The most studied progesterone receptor antagonists are mifepristone (Mifegyne; Roussel-UCLAF; RU486) and ZK98734 and ZK98299 (Schering AG). These compounds bind avidly to the progesterone receptor and glucocorticoid receptor but have essentially no binding to the mineralocortocoid, oestrogen or androgen receptors. Mifepristone also binds avidly to albumin, resulting in a half-life of approximately 24 h after oral administration. Progesterone receptor antagonists can induce menstruation by a direct action upon the endometrium. They have also been shown to exert weak progesterone agonist actions in certain circumstances and to modulate pituitary hormone secretion by antagonizing the feedback actions of progesterone. Moreover, they release prostaglandin F2 alpha and E2 from human endometrium or early pregnancy decidua and reduce the metabolism of these eicosanoids. Clinically, progesterone receptor antagonists have been used in trials of menstrual regulation, abortion and induction of labour, and during treatment of breast or ovarian cancer, some forms of hypertension and meningioma. Progesterone receptor antagonists have been administered to approximately 70,000 women in 18 countries as medical abortifacients. They have been proven, especially when combined with prostaglandin analogues, to be as effective as surgical methods of termination of pregnancy. Progesterone receptor antagonists have focussed international attention on menstrual regulation, abortion and the rights of women to regulate their fertility.
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Kociszewska, Karolina, and Piotr Czekaj. "New Insight into Progesterone-dependent Signalization." Open Pharmaceutical Sciences Journal 4, no. 1 (February 16, 2017): 11–22. http://dx.doi.org/10.2174/1874844901704010011.
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Background: Various effects of steroid hormone activity cannot easily be explained by the action of classical nuclear receptors and genomic signal transduction pathways. These activities are manifested principally as rapid processes, lasting from seconds to minutes, resulting in changes in ion transduction, calcium intracellular concentration, and level of the second messengers, which cannot be realized through the genomic pathway. Hence, it has been proposed that other kinds of mediators should be involved in steroid-induced processes, namely receptors located on the cell surface. The search for their chemical nature and role is of utmost importance. Current state of knowledge confirms their relation to GPCRs. Moreover, it seems that almost every nuclear receptor specific for steroid hormone family has its membrane-bound equivalent. Objective: In this review, we summarize current state of knowledge about nuclear and membrane receptors for progesterone, and describe their potential functions alone, as well as in cooperation with other receptors. Conclusion: In the light of common expression, both in species and organs, membrane receptors could play a role that is at least comparable to nuclear receptors. Further exploration of membrane receptor-dependent signaling pathways could give a new insight in the treatment of many endocrine and oncological pathologies.
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Sundarasamy, Supasakthi, Priyanka P, Vijayalakshmi S, Pradeep Balaji, Jayakumar Murugesan, and Supadevi Sundarasamy. "Expression of Progesterone Receptor in Meningioma: A Tertiary Care Experience." Indian Journal of Pathology: Research and Practice 8, no. 3 (2019): 283–91. http://dx.doi.org/10.21088/ijprp.2278.148x.8319.6.
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Martel, D., M. N. Monier, D. Roche, V. J. De Feo, and A. Psychoyos. "Hormonal dependence of the metrial gland: further studies on oestradiol and progesterone receptor levels in the rat." Journal of Endocrinology 120, no. 3 (March 1989): 465–72. http://dx.doi.org/10.1677/joe.0.1200465.
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ABSTRACT The main objective of the present study was to analyse the hormonal dependence of the metrial gland formed in pseudopregnant animals following massive decidualization. On day 13 of pseudopregnancy (when the metrial gland reaches its maximal development) animals were ovariectomized and given s.c. implants of oestradiol and/or progesterone. A new implant technique for oestradiol delivery is described which provides circulating concentrations of oestradiol in the physiological range. In addition, we extended our previous work concerning oestradiol receptor and progesterone receptor concentrations in the metrial gland of pseudopregnant rats. The low oestradiol receptor concentration which we previously reported up to day 17 was maintained until the end of pseudopregnancy (day 21–1·5 fmol/μg DNA), whereas the progesterone receptor concentration remained raised (≃3·5 fmol/μg DNA) from day 13 to day 19 and then decreased on day 21. The correlation of metrial gland weight and kinetics of the tissue oestradiol and progesterone receptors contents with the circulating oestradiol and progesterone concentrations lead to the following conclusions. First, the maintenance of the metrial gland is strictly progesterone-dependent. It is unlike the deciduoma which regresses spontaneously, even in the presence of progesterone. Secondly, the production of oestradiol receptor, but not of progesterone receptor, appears to be repressed in the metrial gland under the influence of progesterone. Thus, the tissue retains its ability to respond to progesterone because of a high concentration of progesterone receptor. It is difficult to attribute this high tissue progesterone receptor concentration to oestradiol stimulation since, even at low levels, oestradiol induces tissue regression. We suggest that the high progesterone receptor concentration could be due to constitutive (basal) progesterone receptor production. Journal of Endocrinology (1989) 120, 465–472
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Olbrich, Laura, Lisa Wessel, Ajeesh Balakrishnan-Renuka, Marion Böing, Beate Brand-Saberi, and Carsten Theiss. "Rapid Impact of Progesterone on the Neuronal Growth Cone." Endocrinology 154, no. 10 (October 1, 2013): 3784–95. http://dx.doi.org/10.1210/en.2013-1175.
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In the last two decades, sensory neurons and Schwann cells in the dorsal root ganglia (DRG) were shown to express the rate-limiting enzyme of the steroid synthesis, cytochrome P450 side-chain cleavage enzyme (P450scc), as well as the key enzyme of progesterone synthesis, 3β-hydroxysteroid dehydrogenase (3β-HSD). Thus, it was well justified to consider that DRG neurons similarly are able to synthesize progesterone de novo from cholesterol. Because direct progesterone effects on axonal outgrowth in peripheral neurons have not been investigated up to now, the present study provides the first insights into the impact of exogenous progesterone on axonal outgrowth in DRG neurons. Our studies including microinjection and laser scanning microscopy demonstrate morphological changes especially in the neuronal growth cones after progesterone treatment. Furthermore, we were able to detect a distinctly enhanced motility only a few minutes after the start of progesterone treatment using time-lapse imaging. Investigation of the cytoskeletal distribution in the neuronal growth cone before, during, and after progesterone incubation revealed a rapid reorganization of actin filaments. To get a closer idea of the underlying receptor mechanisms, we further studied the expression of progesterone receptors in DRG neurons using RT-PCR and immunohistochemistry. Thus, we could demonstrate for the first time that classical progesterone receptor (PR) A and B and the recently described progesterone receptor membrane component 1 (PGRMC1) are expressed in DRG neurons. Antagonism of the classical progesterone receptors by mifepristone revealed that the observed progesterone effects are transmitted through PR-A and PR-B.
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Krakowska, Izabela, and Grzegorz Lonc. "Expression of Progesterone Receptors in Hippocampal Neurons in Rabbit Males." Bulletin of the Veterinary Institute in Pulawy 56, no. 2 (June 1, 2012): 231–34. http://dx.doi.org/10.2478/v10213-012-0041-1.
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Abstract The aim of this study was to investigate the presence of progesterone receptors in hippocampal neurons of male rabbits and the distribution of these receptors in different areas of the hippocampus. The examinations were carried out on brains of five males, New Zealand breed, age of 2 years, weighing 2-3 kg. Immunohistochemical detection of receptors was performed using DAKO LSAB + Kit Peroxidase method. The sections were incubated with primary monoclonal antibody for progesterone receptor NCL-LPGR- AB. The obtained results have shown the presence of progesterone receptors in neurons of CA1, CA3, and CA4 regions of the hippocampus. The reaction also occurred in the region of granular cells of the dental gyrus. The reaction was seen in the cytoplasm and nuclei of neurons simultaneously, whereas some neurons did not show any reaction in the nucleus and cytoplasm. Occurrence of progesterone receptors in most neurons of the hippocampus confirms a direct influence of progesterone on the hippocampus and its functions in rabbit males.
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Sadan, O., B. Van Iddekinge, C. J. Van Gelderen, N. Savage, P. J. Becker, L. A. Van Der Walt, and M. Robinson. "Oestrogen and Progesterone Receptor Concentrations in Leiomyoma and Normal Myometrium." Annals of Clinical Biochemistry: International Journal of Laboratory Medicine 24, no. 3 (May 1987): 263–67. http://dx.doi.org/10.1177/000456328702400304.
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The content of cytoplasmic 17β oestradiol and progesterone receptors in human uterine leiomyoma and normal myometrium in the Negroid population was determined. Eighteen women of reproductive age, at various stages of the menstrual cycle, were included in the study. The serum oestrogen and progesterone concentrations were also measured. This is the first report in the literature in which oestrogen and progesterone receptors in leiomyoma are significantly higher than in normal myometrium ( P=0·0002). The steroid dependence of the growth of leiomyomas may be related to the steroid receptor level. The presence of persistently high concentrations of oestrogen and progesterone receptors in leiomyoma should be helpful in the treatment of this benign tumour.
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Drobintseva, Anna O., A. E. Andreev, V. O. Polyakova, and I. M. Kvetnoy. "Endometriosis disease: the patogenetic role of hormone resepters and methods of diagnosis." Clinical Medicine (Russian Journal) 96, no. 9 (December 30, 2018): 796–803. http://dx.doi.org/10.18821/0023-2149-2018-96-9-796-803.
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This review summarizes current literature data taken from the information bases of elibrary and pubmed, on hormone receptors, which participate or have a significant impact on the pathogenesis of endometrial disease according to new data sources. They include estrogen receptors (ERa; ERe), progesterone receptors (PRA; PRB), prolactin receptors (PLR), anti-mullerian hormone receptor (AMHR2), kisspeptin receptor (KISS1R) and melatonin receptor (MR). It was established that expression of ERe genes is up-regulated in heterotopy, whereas ERa expression is lower compared to normal tissue. The progesterone receptor is of great interest for study because of inconsistent data on its expression. Receptors for anti-mullerian hormone hormone is no less significant in the study of the pathogenesis of the disease, since AMH stimulates apoptosis in endometrioid cells, limiting their expansion. The most controversial role in endometriosis belongs to prolactin receptors, some authors believe that in endometriosis, a decrease in expression of PLR is observed, while in other articles an increase of expression is postulated. It has been shown that in patients with endometriosis, the expression of the KISS1R is reduced in the endometrium. The data on the expression of melatonin and its receptors in endometriosis is absence.
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Ide, Hiroki, and Hiroshi Miyamoto. "Steroid Hormone Receptor Signals as Prognosticators for Urothelial Tumor." Disease Markers 2015 (2015): 1–12. http://dx.doi.org/10.1155/2015/840640.
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There is a substantial amount of preclinical or clinical evidence suggesting that steroid hormone receptor-mediated signals play a critical role in urothelial tumorigenesis and tumor progression. These receptors include androgen receptor, estrogen receptors, glucocorticoid receptor, progesterone receptor, vitamin D receptor, retinoid receptors, peroxisome proliferator-activated receptors, and others including orphan receptors. In particular, studies using urothelial cancer tissue specimens have demonstrated that elevated or reduced expression of these receptors as well as alterations of their upstream or downstream pathways correlates with patient outcomes. This review summarizes and discusses available data suggesting that steroid hormone receptors and related signals serve as biomarkers for urothelial carcinoma and are able to predict tumor recurrence or progression.
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Markicevic, Milan, Natasa Todorovic-Rakovic, Ksenija Kanjer, and Dragica Nikolic-Vukosavljevic. "The importance of simultaneous determination of breast cancer biomarkers." Archive of Oncology 10, no. 3 (2002): 165–67. http://dx.doi.org/10.2298/aoo0203165m.
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It is shown that steroid hormone receptors by themselves are not sufficiently strong prognostic factors in management of breast cancer. For that reason, simultaneous consideration of different biomarkers seems to be more appropriate for clinical use, i.e. selections of patients with high/inter-mediate/low risk of disease outcome. However, the amount of tumor material available from breast carcinoma can preclude determination of estrogen- regulated biomarkers together with estrogen receptor and progesterone receptor. The aim of this study was to assess the possibility of estrogen receptor and progesterone receptor determination by a single-point instead of five-point biochemical method. Our results demonstrated that the correlation between measurements of estrogen and progesterone receptor contents obtained by the five-point and single-point assay in the total population was very high. Consequently, we could use the single-point assay instead of five-point assay for estrogen receptor and progesterone receptor determination, thus making possible determination of other molecular biomarkers from the same breast carcinoma.
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Vaillancourt, P., S. Omer, R. Palfree, DR Varma, and S. Mulay. "Downregulation of adrenal atrial natriuretic peptide receptor mRNAs and proteins by pregnancy in rats." Journal of Endocrinology 155, no. 3 (December 1, 1997): 523–30. http://dx.doi.org/10.1677/joe.0.1550523.
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The main objective of this study was to find out if the reported changes in the aldosterone-suppressant activity of atrial natriuretic peptide (ANP) during different hormonal states in rats are due to a modulation of ANP receptors. In zona glomerulosa cells, ribonuclease protection assay detected mRNAs for guanylate cyclase (GC)-coupled ANP GC-A and GC-B receptors, and for ANP C receptors, which are not coupled to GC. Western analysis using polyclonal anti-GC-A and anti-GC-B receptor antibodies revealed the presence of GC-A but not GC-B receptor proteins in zona glomerulosa cells. Pregnancy (days 7, 16 and 21), oestradiol-17 beta and progesterone decreased mRNAs for all the three ANP receptors in zona glomerulosa cells. Pregnancy decreased GC-A receptor proteins in zona glomerulosa cells, but these recovered to virgin values on day 2 postpartum. ANP receptor mRNAs in zona glomerulosa cells increased by postpartum day 2, but did not reach the values found in virgin rats. Zona fasciculata mainly contained GC-A receptor mRNA. It is concluded that ANP receptors in rat adrenal zona glomerulosa are modulated by pregnancy, oestrogen and progesterone; a decrease in ANP GC-A receptors during pregnancy might explain the accompanying decrease in the aldosterone-suppressant effects of ANP.
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Shramko, S. V., L. F. Gulyaeva, V. N. Zorina, and T. V. Tretyakova. "Proliferative diseases of the uterus: clinical, immunological, and molecular aspects." Voprosy ginekologii, akušerstva i perinatologii 19, no. 5 (2020): 13–21. http://dx.doi.org/10.20953/1726-1678-2020-5-13-21.
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Objective. To perform comparative analysis of clinical data, serum levels of acute-phase proteins, cytokines, steroid hormones, and expression of genes encoding sex hormone receptors in tissues of patients with proliferative diseases of the uterus. Patients and methods. We analyzed clinical data of 349 patients with various proliferative diseases of the uterus. We also evaluated their serum levels of α2-macroglobulin, pregnancy-associated α2-glycoprotein, their immunocomplexes with IgG, lactoferrin, VEGF, IL-6, TNFa, IL-8, and sex hormones. Uterine tissue samples were tested for the expression of genes encoding estrogen receptors α and β (ЕRα, ЕRβ) and progesterone receptors (PGR). Data analysis was performed using the statistical packages of SAS 9.4, STATISTICA12, and IBM-SPSS Statistics 22. Results. The changes in the level of acute-phase proteins indicated inflammation. In isolated uterine fibroids, expression of genes encoding progesterone receptors prevailed, whereas in isolated adenomyosis, expression of genes encoding estrogen receptors prevailed. Patients with both uterine fibroids and adenomyosis demonstrated similar levels of expression of genes encoding sex steroid hormone receptors. Tissues of uterine leiomyosarcoma were characterized by downregulated expression of genes encoding sex steroid hormone receptors. Conclusion. Upregulation of genes encoding progesterone receptors in isolated uterine fibroids confirms that therapy with progesterone receptor blockers is appropriate in this case. The predominance of expression of genes encoding estrogen receptors in isolated adenomyosis indicates local hyperestrogenism, justifying the use of progestogens and antiestrogens. Equal expression of genes encoding estrogen and progesterone receptors in patients with combined disease, as wells as high frequency of inflammatory changes in tissues and increased serum levels of inflammatory markers, proves the need for antiinflammatory therapy. Key words: adenomyosis, inflammation, steroid receptor genes, leiomyosarcoma, uterine fibroids, gene expression
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Khan, Anum. "GATA3 - IS IT A PROGNOSTIC MARKER IN BREAST CARCINOMA?" International Journal of Advanced Research 9, no. 01 (January 31, 2021): 1008–12. http://dx.doi.org/10.21474/ijar01/12382.
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GATA binding proteins are among the new prognostic factors being explored. My area of interest is GATA3 to correlate it with tumor size, nodal status ,tumor grade, Estrogen receptor, Progesterone receptor and HER2neu receptors in breast carcinoma patients This was a quantitative correlational study Patient were enrolled using consecutive non probability sampling method. GATA3 was inversely related with tumor size ,nodal status and grade. Estrogen positivity was associated with higher GATA3. However Progesterone and HER2Neu receptors statuses did not show any significant association with GATA3 levels. This study concludes that GATA3 expression can be used as a prognostic marker of breast cancer.
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Schumacher, M., H. Coirini, M. Frankfurt, and B. S. McEwen. "Localized actions of progesterone in hypothalamus involve oxytocin." Proceedings of the National Academy of Sciences 86, no. 17 (September 1989): 6798–801. http://dx.doi.org/10.1073/pnas.86.17.6798.
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Two ovarian hormones, estradiol and progesterone, which facilitate mating behavior in the female rat by acting on the ventromedial nuclei (VMN) of the hypothalamus, induce changes in oxytocin receptor binding in this brain region. Estradiol induced a 4-fold increase in the oxytocin receptor binding of the VMN and surrounding area and increased the number and immunostaining of oxytocin fibers in an area lateral to the ventral VMN. Progesterone, in estrogen-primed rats, caused the induced oxytocin receptors to spread over the area containing the oxytocin fibers. Infusion of oxytocin into the ventromedial hypothalamus increased the display of lordosis behavior only in females primed with both estradiol benzoate and progesterone. Thus, the sequential actions of two ovarian hormones bring a neuropeptide and its receptors into register and enable the neuropeptide to exert behavioral effects.
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Vaßen, Lothar, Wojciech Wegrzyn, and Ludger Klein-Hitpass. "Human Insulin Receptor Substrate-2 (IRS-2) Is a Primary Progesterone Response Gene." Molecular Endocrinology 13, no. 3 (March 1, 1999): 485–94. http://dx.doi.org/10.1210/mend.13.3.0256.
Full textAbstract:
Abstract Elevated cAMP has been shown to unmask agonist activity of antiprogestin/antiglucocorticoid RU486. In our search for cellular target genes induced through this cross-talk mechanism, we identified human insulin receptor substrate-2 (IRS-2), a cytoplasmic signaling molecule that mediates effects of insulin, insulin-like growth factor-1 (IGF-I), and other cytokines by acting as a molecular adaptor between diverse receptor tyrosine kinases and downstream effectors. Our analysis of the regulation of IRS-2 in HeLa cell models shows that synergistic induction of IRS-2 by cAMP and RU486 can be mediated by progesterone receptors (PR) and glucocorticoid receptors (GR) and occurs through a relative slow mechanism that requires ongoing protein synthesis. Importantly, we demonstrate that IRS-2 mRNA is also inducible by progesterone, while glucocorticoid effects are only observed in the presence of cAMP. Up-regulation of IRS-2 by progesterone depends strictly on the presence of PR and occurs through a rapid mechanism, suggesting that it represents a primary transcriptional response. Furthermore, we show that expression of IRS-1, which also binds to receptors of insulin, IGF-I, and cytokines, is unaffected by progesterone. Thus, our results demonstrate that progesterone alters the ratio of IRS-1 and IRS-2 in PR-positive cells and implicate a mechanism through which progesterone can modulate the effects of insulin, IGF-I, and cytokines on cell proliferation, differentiation, and homeostasis.
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Pinto, A. E., S. André, E. Mendonça, G. Silva, and J. Soares. "Overall Survival in Advanced Breast Cancer: Relevance of Progesterone Receptor Expression and DNA Ploidy in Fine-Needle Aspirates of 392 Patients." International Journal of Biological Markers 18, no. 1 (January 2003): 7–12. http://dx.doi.org/10.1177/172460080301800102.
Full textAbstract:
Fine-needle aspiration cytology (FNAC) is essential for making a diagnosis in advanced breast cancer. The determination of hormone receptors in the material obtained is useful for predicting patient response to endocrine therapy, but the prognostic value of hormone receptor expression as well as the clinical utility of DNA flow cytometry are controversial. The aim of this prospective study with long-term follow-up (median: 81 months) was to evaluate these biomarkers in relation to overall survival in a series of 392 patients with advanced breast cancer (stage IIB, n=106; IIIA, n=66; IIIB, n=174; and IV, n=46) using FNAC. Estrogen and progesterone receptor expression was found in 65.1% and 46.1% of the tumors, respectively. Hormone receptors were not found to be associated with clinical staging. DNA aneuploidy was present in 70.9% of the cases and the median S-phase fraction (SPF) was 9.4%. There was a significant correlation of aneuploidy and high SPF with lack of hormone receptors. In univariate analysis, advanced disease stage, absence of hormone receptors, DNA aneuploidy and high SPF showed a statistically significant correlation with poor clinical outcome. In multivariate analysis, disease stage, progesterone receptors and DNA ploidy retained independent prognostic significance in relation to overall survival. These data indicate that progesterone receptor expression and DNA ploidy are independent prognostic factors in advanced breast cancer.
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Okulicz, W. C. "Temporal effects of progesterone inhibition of occupied nuclear oestrogen receptor retention in the rat uterus." Journal of Endocrinology 121, no. 1 (April 1989): 101–7. http://dx.doi.org/10.1677/joe.0.1210101.
Full textAbstract:
ABSTRACT Previous studies have shown that progesterone rapidly inhibits retention of uterine nuclear oestrogen receptor in several mammalian species. This effect of progesterone may constitute a general mechanism by which progesterone modulates oestrogen action. The objective of the present study was to examine the temporal pattern of progesterone inhibition of retention of occupied nuclear oestrogen receptors in the rat uterus at various sustained serum concentrations of progesterone. Silicone elastomer implants (1 cm) packed with crystalline oestrogen were placed s.c. in the flank region of ovariectomized adult rats. Twenty-four hours after placement of the implants, animals were either injected s.c. with 5 mg progesterone in corn oil every 24 h, treated with 2 × 5 cm implants of progesterone, or treated with 1 × 5 cm silicone elastomer implants of progesterone. Serum concentrations of progesterone at the time of necropsy were 0·47 ± 0·02, 0·18 ± 0·02 and 0·10 ± 0·01 μmol/l respectively. Control animals were given oestrogen implants alone and had a serum progesterone level of 0·03 ± 0·01 μmol/l. Occupied nuclear oestrogen receptor and cytosolic oestrogen and progesterone receptor levels (pmol/uterus) were measured between 0 and 48 h following progesterone treatment. Cytosolic progesterone receptor levels were suppressed similarly in all progesterone-treated groups compared with controls given oestrogen alone throughout the 48-h test period. Cytosolic oestrogen receptor levels were significantly suppressed at 12 h following progesterone treatment in all groups. Except for the highest (pharmacological) serum progesterone concentration, cytosolic oestrogen receptor exhibited a replenishment phase between 12 and 48 h. Although pharmacological levels of serum progesterone (0·47± 0·02μmol/l) significantly suppressed the level of occupied nuclear oestrogen receptor at 12 h, the level increased subsequently at 24 and 36 h and was equivalent to the control value (oestradiol alone) by 48 h. At a mean serum concentration of 0·18 ± 0·02 or 0·10 ± 0·01 μmol/l, the level of occupied nuclear oestrogen receptor was also suppressed significantly at 12 h, but to a lesser degree. These results show that progesterone decreases the concentration of occupied nuclear oestrogen receptor in the rat uterus and that the duration and extent of suppression of occupied nuclear oestrogen receptor is related to the serum progesterone concentration. Journal of Endocrinology (1989) 121, 101–107
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Rubinstein, Abraham B., David Loven, Abraham Geier, Eli Reichenthal, and Natan Gadoth. "Hormone receptors in initially excised versus recurrent intracranial meningiomas." Journal of Neurosurgery 81, no. 2 (August 1994): 184–87. http://dx.doi.org/10.3171/jns.1994.81.2.0184.
Full textAbstract:
✓ Intracranial meningiomas from 51 surgical patients consecutively treated during an 18-month period were evaluated for the presence of receptors to progesterone and estrogen. Thirty-eight patients underwent initial resection during this time and 13 underwent reoperation for recurrent disease. With positivity defined as receptor levels greater than 10 fmol/mg of cytosol protein, 84% of all the meningiomas were positive for progesterone receptors, whereas only 33% were positive for estrogen receptors. Among the recurrent meningiomas, 92% showed evidence of progesterone receptors and 54% of estrogen receptors; these figures were not significantly different from the corresponding incidence of 82% and 26%, respectively, among the initially excised tumors. However, the mean concentration of progesterone receptors in the recurrent tumor group was significantly higher when compared to the concentration in the initially excised group (p < 0.02). Twenty meningiomas (39%) were considered to be radiation-induced, since they were removed from patients who had received scalp irradiation during childhood. The incidence and concentration of receptors in the radiation-induced tumors were generally comparable to those in the spontaneous meningiomas. This study confirms previous reports of a high incidence of hormone receptors, mainly for progesterone, in meningiomas. In addition, it shows that in recurrent meningiomas these receptors persist and even increase. The results therefore support hormone treatment for nonresectable meningiomas, especially at recurrence.