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Gene Review

Pgr  -  progesterone receptor

Rattus norvegicus

Synonyms: Nr3c3, Nuclear receptor subfamily 3 group C member 3, PR, Progesterone receptor
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Disease relevance of Pgr

  • The ER-mediated repression of the PR immunoreactivity was evidently restricted to the uterine epithelium, as we found that in the epithelial cells of the mammary gland and in cells of N-nitrosomethylurea-induced mammary carcinomas the PR expression was induced by estrogens and was blocked by the pure antiestrogen ZM 182780 [1].
  • These compounds, unable to stimulate proliferation of uterine leiomyoma cells, did exhibit agonistic activity in these cells at the transcriptional level in the estrogen-sensitive reporter gene assay, and they were also able to upregulate PR message [2].
  • The effects of ischemia on estrogen and progesterone receptor profiles in the rodent uterus [3].
  • In MtT/F84, a pituitary tumor, which was established in our laboratory and has been maintained with in vivo passages, we investigated the PR regulation by E2 in relation to the host's thyroidal status [4].
  • Androgen is suggested to act as a negative modulator of progesterone receptor levels, which might have clinical relevance in terms of hormone therapy of breast cancer [5].

Psychiatry related information on Pgr


High impact information on Pgr


Chemical compound and disease context of Pgr


Biological context of Pgr


Anatomical context of Pgr

  • We show herein that E alone does not induce the expression of PR mRNA in preovulatory granulosa cells [16].
  • Taken together, our results suggest that the proliferative response of uterine stromal cells to picomolar concentrations of progestins does not require direct transcriptional effects and is mediated by activation of the Erk1-2 and Akt signaling pathways via cross talk between PR and ERbeta [15].
  • Using electrophoretic mobility shift assays, the consensus ERE was shown to bind ERbeta, the predominant subtype present in rat granulosa cells, and ERalpha, the predominant subtype present in luteal cells, whereas the putative ERE-like region (ERE3) of the proximal PR promoter did not bind either ER subtype [16].
  • Upon progestin treatment PR translocated to the cell nucleus where it colocalized with activated Erk1-2 [15].
  • By use of immunohistochemistry we studied the effects of estrogens on the PR levels in the individual cell types of the target organs uterus and breast [1].

Associations of Pgr with chemical compounds

  • Although 17beta-estradiol (E) can induce PR mRNA and activate PR promoter-reporter constructs in other cell types, the effects of E in granulosa cells appear to be indirect [16].
  • Induction of PR mRNA by forskolin is blocked by the A-kinase inhibitor H89 and cycloheximide but not by the E antagonist, ICI 164,384 [16].
  • In this work, we determined the expression pattern and the hormonal regulation of progesterone receptor (PR) isoforms in the rat lung of ovariectomized female rats after estradiol (E2) and progesterone (P4) treatments [18].
  • The expression of both PR isoforms in the lung at mRNA and at protein levels was up-regulated by E2 while P4 down-regulated it at mRNA level [18].
  • Twenty-four hours after the treatment, the expression of progesterone receptor mRNA in the anterior pituitary and the level of luteinizing hormone (LH), follicle-stimulating hormone, and prolactin were determined [19].

Physical interactions of Pgr


Co-localisations of Pgr


Regulatory relationships of Pgr

  • Tamoxifen and flutamide induced PR and slightly upregulated ERalpha immunoexpression but had only a minor or no effect on AR expression and the stromal:epithelial ratio, though flutamide retarded normal development of the SVs [24].
  • Together, these results indicated that membrane ER-mediated E2 inhibition of the TX-stimulated LHRH self-priming pathway involves a blockade of gonadotrope PR phosphorylation/activation, but not a deficient response of PR to phosphorylases [25].
  • Progesterone receptor mRNA was not detected in rat-1 cells and was induced by E2 in both rat-1 + ERalpha and rat-1 + ERbeta cells [26].
  • Treatment of animals with estrogen induced PR expression in the ERalpha-expressing mammary epithelial cells in the absence of detectable SRC-1 and did not affect the segregated pattern of SRC-1 and ERalpha expression [27].
  • Together, these results suggest that CaT1 is regulated by P4 at diestrus via a PR-dependent pathway [28].

Other interactions of Pgr

  • In the YTS, TEST activated gene transcription in the yeast containing the AR or PR [29].
  • DPN alone had only a significant E-like effect on gonadectomy cells and IR-PR, but not on GnRH self-priming [30].
  • Besides PCNA, GEN effects on the uterine mRNA expression of IGF-1, IGF-1R, Complement C3, estrogen receptor-alpha (ERalpha) and -beta (ERbeta), as well as progesterone receptor were investigated in intact and OVX co-treated animals [31].
  • Drospirenone displayed high affinity to PR and MR and low binding to AR, similar to progesterone [32].
  • ER and PRL-R were low but PgR increased significantly in the tumor of the tamoxifen-treated rats [33].

Analytical, diagnostic and therapeutic context of Pgr


  1. Progesterone receptor repression by estrogens in rat uterine epithelial cells. Parczyk, K., Madjno, R., Michna, H., Nishino, Y., Schneider, M.R. J. Steroid Biochem. Mol. Biol. (1997) [Pubmed]
  2. Estrogenic effects of organochlorine pesticides on uterine leiomyoma cells in vitro. Hodges, L.C., Bergerson, J.S., Hunter, D.S., Walker, C.L. Toxicol. Sci. (2000) [Pubmed]
  3. The effects of ischemia on estrogen and progesterone receptor profiles in the rodent uterus. Bland, K.I., Freedman, B.E., Harris, P.L., He, Y.J., Wittliff, J.L. J. Surg. Res. (1987) [Pubmed]
  4. Blockade of the estrogen induced increase in progesterone receptor caused by propylthiouracil, an anti-thyroid drug, in a transplantable pituitary tumor in rats. Fujimoto, N., Watanabe, H., Ito, A. Endocr. J. (1996) [Pubmed]
  5. Androgen control of cytosol progesterone receptor levels in the MT-W9B transplantable mammary tumor in the rat. Ip, M.M., Milholland, R.J., Kim, U., Rosen, F. J. Natl. Cancer Inst. (1982) [Pubmed]
  6. Neural steroid hormone receptor gene expression in pregnant rats. Mann, P.E., Babb, J.A. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  7. Downregulation of androgen, estrogen and progesterone receptor genes and protein is involved in aging-related erectile dysfunction. Shirai, M., Yamanaka, M., Shiina, H., Igawa, M., Fujime, M., Lue, T.F., Dahiya, R. Int. J. Impot. Res. (2003) [Pubmed]
  8. Natural and synthetic progestins accelerate 7,12-dimethylbenz[a]anthracene-initiated mammary tumors and increase angiogenesis in Sprague-Dawley rats. Benakanakere, I., Besch-Williford, C., Schnell, J., Brandt, S., Ellersieck, M.R., Molinolo, A., Hyder, S.M. Clin. Cancer Res. (2006) [Pubmed]
  9. Progesterone receptor gene and protein expression in the anterior preoptic area and hypothalamus of defeminized rats. Arrieta, I., Díaz-Ibáñez, L.B., Morales, T., Mendoza-Garcés, L., Morimoto, S., Moreno-Mendoza, N., Cerbón, M.A. J. Neurobiol. (2003) [Pubmed]
  10. Glucocorticoid- and progesterone-specific effects are determined by differential expression of the respective hormone receptors. Strähle, U., Boshart, M., Klock, G., Stewart, F., Schütz, G. Nature (1989) [Pubmed]
  11. Effect of the aromatase inhibitor vorozole on estrogen and progesterone receptor content of rat mammary carcinomas induced by 1-methyl-1-nitrosourea. Knott, K.K., McGinley, J.N., Lubet, R.A., Steele, V.E., Thompson, H.J. Breast Cancer Res. Treat. (2001) [Pubmed]
  12. Steroid hormone receptors in the rat mammary adenocarcinoma induced by N-hydroxy-N-2-fluorenylacetamide. Li, S.A., Malejka-Giganti, D., Li, J.J. J. Natl. Cancer Inst. (1982) [Pubmed]
  13. Functionality of estrogen receptor and tamoxifen treatment of R3327 Dunning rat prostate adenocarcinoma. Ip, M.M., Milholland, R.J., Rosen, F. Cancer Res. (1980) [Pubmed]
  14. Effect of ether or ketamine anesthesia on rat uterine estrogen and progesterone receptors. Zarembka, F.R., Koller, D.E., Plotka, E.D. Clin. Chem. (1989) [Pubmed]
  15. Progestin activation of nongenomic pathways via cross talk of progesterone receptor with estrogen receptor beta induces proliferation of endometrial stromal cells. Vallejo, G., Ballaré, C., Barañao, J.L., Beato, M., Saragüeta, P. Mol. Endocrinol. (2005) [Pubmed]
  16. Hormone induction of progesterone receptor (PR) messenger ribonucleic acid and activation of PR promoter regions in ovarian granulosa cells: evidence for a role of cyclic adenosine 3',5'-monophosphate but not estradiol. Clemens, J.W., Robker, R.L., Kraus, W.L., Katzenellenbogen, B.S., Richards, J.S. Mol. Endocrinol. (1998) [Pubmed]
  17. Rat estrogen receptor-alpha and -beta, and progesterone receptor mRNA expression in various prostatic lobes and microdissected normal and dysplastic epithelial tissues of the Noble rats. Lau, K.M., Leav, I., Ho, S.M. Endocrinology (1998) [Pubmed]
  18. Regulation of progesterone receptor isoforms expression by sex steroids in the rat lung. González-Arenas, A., Villamar-Cruz, O., Guerra-Araiza, C., Camacho-Arroyo, I. J. Steroid Biochem. Mol. Biol. (2003) [Pubmed]
  19. Effects of p-Nonylphenol and 4-tert-Octylphenol on the Anterior Pituitary Functions in Adult Ovariectomized Rats. Furuta, M., Funabashi, T., Kawaguchi, M., Nakamura, T.J., Mitsushima, D., Kimura, F. Neuroendocrinology (2006) [Pubmed]
  20. Estrogen-induced transcription of the progesterone receptor gene does not parallel estrogen receptor occupancy. Lee, Y.J., Gorski, J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  21. Effects of injury and progesterone treatment on progesterone receptor and progesterone binding protein 25-Dx expression in the rat spinal cord. Labombarda, F., Gonzalez, S.L., Deniselle, M.C., Vinson, G.P., Schumacher, M., De Nicola, A.F., Guennoun, R. J. Neurochem. (2003) [Pubmed]
  22. Growth regulation of two rat adenocarcinoma cell lines by dexamethasone and progesterone. Joly, E., Vignon, F., Rochefort, H. Breast Cancer Res. Treat. (1981) [Pubmed]
  23. Regulation of progesterone receptor messenger ribonucleic acid in the rat medial preoptic nucleus by estrogenic and antiestrogenic compounds: an in situ hybridization study. Shughrue, P.J., Lane, M.V., Merchenthaler, I. Endocrinology (1997) [Pubmed]
  24. Relationship between expression of sex steroid receptors and structure of the seminal vesicles after neonatal treatment of rats with potent or weak estrogens. Williams, K., Fisher, J.S., Turner, K.J., McKinnell, C., Saunders, P.T., Sharpe, R.M. Environ. Health Perspect. (2001) [Pubmed]
  25. Oestradiol-17beta inhibits tamoxifen-induced LHRH self-priming blocking hormone-dependent and ligand-independent activation of the gonadotrope progesterone receptor in the rat. Sánchez-Criado, J.E., Garrido-Gracia, J.C., Bellido, C., Aguilar, R., Guelmes, P., Abreu, P., Alonso, R., Barranco, I., Millán, Y., de Las Mulas, J.M. J. Endocrinol. (2006) [Pubmed]
  26. Responses to stable ectopic estrogen receptor-beta expression in a rat fibroblast cell line. Cheng, J., Malayer, J.R. Mol. Cell. Endocrinol. (1999) [Pubmed]
  27. Segregation of steroid receptor coactivator-1 from steroid receptors in mammary epithelium. Shim, W.S., DiRenzo, J., DeCaprio, J.A., Santen, R.J., Brown, M., Jeng, M.H. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  28. Differential expression of uterine calcium transporter 1 and plasma membrane Ca2+ ATPase 1b during rat estrous cycle. Kim, H.J., Lee, G.S., Ji, Y.K., Choi, K.C., Jeung, E.B. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  29. Evaluation of a Tier I screening battery for detecting endocrine-active compounds (EACs) using the positive controls testosterone, coumestrol, progesterone, and RU486. O'Connor, J.C., Davis, L.G., Frame, S.R., Cook, J.C. Toxicol. Sci. (2000) [Pubmed]
  30. Biological role of pituitary estrogen receptors ERalpha and ERbeta on progesterone receptor expression and action and on gonadotropin and prolactin secretion in the rat. Sánchez-Criado, J.E., Martín De Las Mulas, J., Bellido, C., Tena-Sempere, M., Aguilar, R., Blanco, A. Neuroendocrinology (2004) [Pubmed]
  31. Combinatorial effects of the phytoestrogen genistein and of estradiol in uterus and liver of female Wistar rats. Diel, P., Hertrampf, T., Seibel, J., Laudenbach-Leschowsky, U., Kolba, S., Vollmer, G. J. Steroid Biochem. Mol. Biol. (2006) [Pubmed]
  32. The novel progestin drospirenone and its natural counterpart progesterone: biochemical profile and antiandrogenic potential. Fuhrmann, U., Krattenmacher, R., Slater, E.P., Fritzemeier, K.H. Contraception. (1996) [Pubmed]
  33. Reduction of estrogen and prolactin receptors in 7,12-dimethylbenz(a)anthracene-induced rat mammary tumor by high doses of estrogen. Shigaki, N., Kimura, M., Takano, S., Fujino, N., Akagi, M. The Japanese journal of surgery. (1987) [Pubmed]
  34. Estrogen target gene regulation and coactivator expression in rat uterus after developmental exposure to the ultraviolet filter 4-methylbenzylidene camphor. Durrer, S., Maerkel, K., Schlumpf, M., Lichtensteiger, W. Endocrinology (2005) [Pubmed]
  35. Effect of estrogens on ontogenetic expression of progesterone receptor in the fetal female rat reproductive tract. Okada, A., Ohta, Y., Buchanan, D., Sato, T., Iguchi, T. Mol. Cell. Endocrinol. (2002) [Pubmed]
  36. Transient expression of progesterone receptor messenger RNA in ovarian granulosa cells after the preovulatory luteinizing hormone surge. Park, O.K., Mayo, K.E. Mol. Endocrinol. (1991) [Pubmed]
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