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Gene Review

Pgr  -  progesterone receptor

Mus musculus

Synonyms: 9930019P03Rik, BB114106, ENSMUSG00000074510, NR3C3, Nr3c3, ...
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Disease relevance of Pgr


Psychiatry related information on Pgr

  • These results suggest that androgens may interact with either AR or PR, and perhaps both receptors, in E2 + TP-induced mammary glands and the induced tumors to effect the reduction in latency period, enhance tumor size, and increase incidence to 100% [6].

High impact information on Pgr


Chemical compound and disease context of Pgr


Biological context of Pgr

  • The identification of two regulated proteases in the ovary, together with their abnormal expression in anovulatory PR knockout mice, suggests that each plays a critical role in follicular rupture and represents a major advance in our understanding of the proteolytic events that control ovulation [14].
  • The PR-A and PR-B isoforms are both detected on Western blot, and the ratio of isoforms is the same in both genotypes [15].
  • We conclude that SRC-2 is appropriated by PR in a subset of transcriptional cascades obligate for normal uterine and mammary morphogenesis and function [16].
  • Progesterone receptor (PR), a ligand-activated transcription factor, is a key regulator of cellular proliferation and differentiation in reproductive tissues [17].
  • Surprisingly, one of the earliest changes in gene expression in response to a differentiation signal observed is PR gene induction [18].

Anatomical context of Pgr

  • In the BERKO uterus, E(2) induced PR in the stroma but did not down-regulate it in the epithelium [19].
  • As expected, E(2) increased PR in the stroma and decreased it in the luminal epithelium of wild-type mice [19].
  • Progesterone receptor mRNA was not detectable until the blastocyst stage [20].
  • In the case of the mammary gland, whole-mount and histological analysis disclosed the absence of significant ductal side branching and alveologenesis in the hormone-treated PR(Cre/+) SRC-2(flox/flox) mammary gland, reinforcing an important role for SRC-2 in cellular proliferative changes that require PR [16].
  • In the early pregnant uterus, Bteb1 expression in stromal cells temporally coincides with PR-A isoform-dependent decidual formation at the time of implantation [17].

Associations of Pgr with chemical compounds

  • These results indicate that estrogen receptor alpha modulation of PR levels is not necessary for expression of the PR or genomic and physiologic responses to progesterone in the ERKO uterus [15].
  • The estrogen receptor alpha knockout (ERKO) mouse uterus was observed to express PR mRNA that cannot be induced by estrogen [15].
  • Recruitment was disrupted by cotreatment with progestin and PRL, suggesting a mutual interference between activated PR and Stat5a [21].
  • Coordinate transcription of the ADAMTS-1 gene by luteinizing hormone and progesterone receptor [22].
  • Forskolin plus phorbol myristate acetate also increased promoter activity and, when added to cells cotransfected with PRA, ADAMTS-1 promoter activity increased further [22].
  • PRA was the predominant PR isoform expressed during sidebranching, and colocalization of PRA with 5-bromo-2'-deoxyuridine revealed that proliferation of PRA-positive and -negative cells was responsible for P-induced sidebranching [23].

Physical interactions of Pgr


Regulatory relationships of Pgr


Other interactions of Pgr

  • The spatial and temporal separation of PR isoform expression in mouse mammary gland provides a unique opportunity to determine the specific functions of PRA vs. PRB in vivo [29].
  • These findings suggest that estrogen induces stromal PR via ERbeta in alphaERKO uterus [33].
  • The whole-uterus level of PR and Hoxa10 mRNAs did not vary; however, the PR protein was induced in the stroma 24 h after oil infusion [34].
  • Ribonuclease protection analyses showed that ovarian progesterone receptor and androgen receptor mRNA expression were similar in the two groups [35].
  • As a result, betaERKO ovaries were unable to fully respond to an ovulatory bolus of gonadotropin, leading to a reduced rate of follicle rupture; insufficient induction of prostaglandin-synthase 2 and progesterone receptor; an aberrant increase in aromatase activity and plasma estradiol; and incomplete expansion of the cumulus-oocyte complex [36].

Analytical, diagnostic and therapeutic context of Pgr

  • Progesterone Receptor Repression of Prolactin/Signal Transducer and Activator of Transcription 5-Mediated Transcription of the {beta}-Casein Gene in Mammary Epithelial Cells [21].
  • The results of Northern and in situ hybridization demonstrated increased uterine levels of PR and LF messenger RNAs (mRNAs) by all of these xenobiotics, but quantitatively the responses were much lower than those induced by E2 or 4-OH-E2 [37].
  • Interestingly, immunohistochemistry indicated that the induction of apoptosis by PR antagonists was predominant in the epithelium, whereas increase in PR protein expression was observed in stromal cells of both tissues [38].
  • In organ cultures of alphaERKO uterus, both E(2) and diethylstilbestrol induced stromal PR, and ICI inhibited this induction [33].
  • In previous studies, using high-density DNA microarray analysis, we identified a subset of genes whose expression is repressed by chronic P4-PGR activation in the uterus [31].


  1. Anthrax lethal factor represses glucocorticoid and progesterone receptor activity. Webster, J.I., Tonelli, L.H., Moayeri, M., Simons, S.S., Leppla, S.H., Sternberg, E.M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  2. Expression of progesterone receptor B is associated with G0/G1 arrest of the cell cycle and growth inhibition in NIH3T3 cells. Horiuchi, S., Kato, K., Suga, S., Takahashi, A., Ueoka, Y., Arima, T., Nishida, J., Hachisuga, T., Kawarabayashi, T., Wake, N. Exp. Cell Res. (2005) [Pubmed]
  3. Steroid hormone receptor status of mouse mammary stem cells. Asselin-Labat, M.L., Shackleton, M., Stingl, J., Vaillant, F., Forrest, N.C., Eaves, C.J., Visvader, J.E., Lindeman, G.J. J. Natl. Cancer Inst. (2006) [Pubmed]
  4. Characterization of transiently and constitutively expressed progesterone receptors: evidence for two functional states. Smith, C.L., Wolford, R.G., O'Neill, T.B., Hager, G.L. Mol. Endocrinol. (2000) [Pubmed]
  5. Increased DNA binding of the estrogen receptor in an estrogen-resistant mammary cancer. Baskevitch, P.P., Vignon, F., Bousquet, C., Rochefort, H. Cancer Res. (1983) [Pubmed]
  6. Promotion of estrogen-induced mammary gland carcinogenesis by androgen in the male Noble rat: probable mediation by steroid receptors. Liao, D.Z., Pantazis, C.G., Hou, X., Li, S.A. Carcinogenesis (1998) [Pubmed]
  7. Progesterone receptor stimulates transcription of mouse mammary tumour virus in a cell-free system. Kalff, M., Gross, B., Beato, M. Nature (1990) [Pubmed]
  8. Subgroup of reproductive functions of progesterone mediated by progesterone receptor-B isoform. Mulac-Jericevic, B., Mullinax, R.A., DeMayo, F.J., Lydon, J.P., Conneely, O.M. Science (2000) [Pubmed]
  9. FK506-Binding Protein 52 Is Essential to Uterine Reproductive Physiology Controlled by the Progesterone Receptor A Isoform. Yang, Z., Wolf, I.M., Chen, H., Periyasamy, S., Chen, Z., Yong, W., Shi, S., Zhao, W., Xu, J., Srivastava, A., S??nchez, E.R., Shou, W. Mol. Endocrinol. (2006) [Pubmed]
  10. Evidence for two progesterone receptor binding sites in murine mammary carcinomas. Helguero, L.A., Lamb, C., Molinolo, A.A., Lanari, C. J. Steroid Biochem. Mol. Biol. (2003) [Pubmed]
  11. Differential effects of raloxifene, tamoxifen and fulvestrant on a murine mammary carcinoma. Lamb, C.A., Helguero, L.A., Fabris, V., Lucas, C., Molinolo, A.A., Lanari, C. Breast Cancer Res. Treat. (2003) [Pubmed]
  12. Cytogenetic findings, Trp53 mutations, and hormone responsiveness in a medroxyprogesterone acetate induced murine breast cancer model. Fabris, V.T., Benavides, F., Conti, C., Merani, S., Lanari, C. Cancer Genet. Cytogenet. (2005) [Pubmed]
  13. Genes regulated by estrogen in breast tumor cells in vitro are similarly regulated in vivo in tumor xenografts and human breast tumors. Creighton, C.J., Cordero, K.E., Larios, J.M., Miller, R.S., Johnson, M.D., Chinnaiyan, A.M., Lippman, M.E., Rae, J.M. Genome Biol. (2006) [Pubmed]
  14. Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases. Robker, R.L., Russell, D.L., Espey, L.L., Lydon, J.P., O'Malley, B.W., Richards, J.S. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  15. Disruption of estrogen signaling does not prevent progesterone action in the estrogen receptor alpha knockout mouse uterus. Curtis, S.W., Clark, J., Myers, P., Korach, K.S. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  16. Steroid receptor coactivator 2 is critical for progesterone-dependent uterine function and mammary morphogenesis in the mouse. Mukherjee, A., Soyal, S.M., Fernandez-Valdivia, R., Gehin, M., Chambon, P., Demayo, F.J., Lydon, J.P., O'Malley, B.W. Mol. Cell. Biol. (2006) [Pubmed]
  17. Subfertility, uterine hypoplasia, and partial progesterone resistance in mice lacking the Kruppel-like factor 9/basic transcription element-binding protein-1 (Bteb1) gene. Simmen, R.C., Eason, R.R., McQuown, J.R., Linz, A.L., Kang, T.J., Chatman, L., Till, S.R., Fujii-Kuriyama, Y., Simmen, F.A., Oh, S.P. J. Biol. Chem. (2004) [Pubmed]
  18. Differentiation of murine embryonic stem cells induces progesterone receptor gene expression. Sauter, C.N., McDermid, R.L., Weinberg, A.L., Greco, T.L., Xu, X., Murdoch, F.E., Fritsch, M.K. Exp. Cell Res. (2005) [Pubmed]
  19. Estrogen receptor (ER) beta, a modulator of ERalpha in the uterus. Weihua, Z., Saji, S., Mäkinen, S., Cheng, G., Jensen, E.V., Warner, M., Gustafsson, J.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  20. Estrogen receptor and progesterone receptor genes are expressed differentially in mouse embryos during preimplantation development. Hou, Q., Gorski, J. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  21. Progesterone Receptor Repression of Prolactin/Signal Transducer and Activator of Transcription 5-Mediated Transcription of the {beta}-Casein Gene in Mammary Epithelial Cells. Buser, A.C., Gass-Handel, E.K., Wyszomierski, S.L., Doppler, W., Leonhardt, S.A., Schaack, J., Rosen, J.M., Watkin, H., Anderson, S.M., Edwards, D.P. Mol. Endocrinol. (2007) [Pubmed]
  22. Coordinate transcription of the ADAMTS-1 gene by luteinizing hormone and progesterone receptor. Doyle, K.M., Russell, D.L., Sriraman, V., Richards, J.S. Mol. Endocrinol. (2004) [Pubmed]
  23. Differential hormonal regulation and function of progesterone receptor isoforms in normal adult mouse mammary gland. Aupperlee, M.D., Haslam, S.Z. Endocrinology (2007) [Pubmed]
  24. Developmental and hormonal regulation of progesterone receptor A-form expression in female mouse lung in vivo: interaction with glucocorticoid receptors. Shao, R., Egecioglu, E., Weijdeg??rd, B., Ljungstr??m, K., Ling, C., Fernandez-Rodriguez, J., Billig, H. J. Endocrinol. (2006) [Pubmed]
  25. Molecular cloning, sequence analyses, and expression of complementary DNA encoding murine progesterone receptor. Schott, D.R., Shyamala, G., Schneider, W., Parry, G. Biochemistry (1991) [Pubmed]
  26. Interplay of steroid hormone receptors and transcription factors on the mouse mammary tumor virus promoter. Truss, M., Chalepakis, G., Beato, M. J. Steroid Biochem. Mol. Biol. (1992) [Pubmed]
  27. Spatio-temporal expression and regulation of dermatopontin in the early pregnant mouse uterus. Kim, H.S., Cheon, Y.P. Mol. Cells (2006) [Pubmed]
  28. The distribution of estrogen receptor-beta mRNA in forebrain regions of the estrogen receptor-alpha knockout mouse. Shughrue, P., Scrimo, P., Lane, M., Askew, R., Merchenthaler, I. Endocrinology (1997) [Pubmed]
  29. Progesterone receptor isoforms A and B: temporal and spatial differences in expression during murine mammary gland development. Aupperlee, M.D., Smith, K.T., Kariagina, A., Haslam, S.Z. Endocrinology (2005) [Pubmed]
  30. Sex specific expression of progesterone receptor in mouse lower urinary tract. Savolainen, S., Santti, R., Streng, T., Gustafsson, J.A., Härkönen, P., Mäkelä, S. Mol. Cell. Endocrinol. (2005) [Pubmed]
  31. Steroid hormone regulation of Clca3 expression in the murine uterus. Jeong, J.W., Lee, K.Y., Lydon, J.P., DeMayo, F.J. J. Endocrinol. (2006) [Pubmed]
  32. Heregulin induces transcriptional activation of the progesterone receptor by a mechanism that requires functional ErbB-2 and mitogen-activated protein kinase activation in breast cancer cells. Labriola, L., Salatino, M., Proietti, C.J., Pecci, A., Coso, O.A., Kornblihtt, A.R., Charreau, E.H., Elizalde, P.V. Mol. Cell. Biol. (2003) [Pubmed]
  33. Regulation of progesterone receptors and decidualization in uterine stroma of the estrogen receptor-alpha knockout mouse. Kurita, T., Lee, K., Saunders, P.T., Cooke, P.S., Taylor, J.A., Lubahn, D.B., Zhao, C., Mäkelä, S., Gustafsson, J.A., Dahiya, R., Cunha, G.R. Biol. Reprod. (2001) [Pubmed]
  34. Studies using the estrogen receptor alpha knockout uterus demonstrate that implantation but not decidualization-associated signaling is estrogen dependent. Curtis Hewitt, S., Goulding, E.H., Eddy, E.M., Korach, K.S. Biol. Reprod. (2002) [Pubmed]
  35. Targeted disruption of the estrogen receptor-alpha gene in female mice: characterization of ovarian responses and phenotype in the adult. Schomberg, D.W., Couse, J.F., Mukherjee, A., Lubahn, D.B., Sar, M., Mayo, K.E., Korach, K.S. Endocrinology (1999) [Pubmed]
  36. Estrogen receptor-beta is critical to granulosa cell differentiation and the ovulatory response to gonadotropins. Couse, J.F., Yates, M.M., Deroo, B.J., Korach, K.S. Endocrinology (2005) [Pubmed]
  37. Differential spatiotemporal regulation of lactoferrin and progesterone receptor genes in the mouse uterus by primary estrogen, catechol estrogen, and xenoestrogen. Das, S.K., Tan, J., Johnson, D.C., Dey, S.K. Endocrinology (1998) [Pubmed]
  38. Nuclear progesterone receptor A and B isoforms in mouse fallopian tube and uterus: implications for expression, regulation, and cellular function. Shao, R., Weijdegård, B., Ljungström, K., Friberg, A., Zhu, C., Wang, X., Zhu, Y., Fernandez-Rodriguez, J., Egecioglu, E., Rung, E., Billig, H. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
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