Taiwanese Journal of Obstetrics and Gynecology
Volume 44, Issue 1 , Pages 16-25, March 2005

Role of Sex Hormone Receptors in Ovulation

  • Peng-Hui Wang

      Affiliations

    • Corresponding Author InformationCorrespondence to: Dr. Peng-Hui Wang, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital and National Yang-Ming University, 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital and Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

Received 23 August 2004; received in revised form 20 September 2004; accepted 20 September 2004.

Article Outline

Summary

Sex hormones including progestins, androgens, and estrogens produced de novo from cholesterol within the ovary play important roles in the growth and differentiation of reproductive tissues and in the maintenance of fertility. Sex hormone effects are often mediated through the sex hormone receptors (SRs). SRs, members of the steroid receptor superfamily, function as sex hormone-dependent transcriptional regulators. After binding the ligand, the activated SR is able to recognize palindromic DNA sequences, called sex hormone response elements, and form a complex with SR-associated proteins to induce the expression of SR target genes. The precise role of sex hormones in follicular development and ovulation remains to be elucidated. The data presented here arise from studies designed to resolve this issue. The use of gene-targeting technology and transgenic techniques to disrupt the genes encoding several members of the SR family, including progesterone receptor A, progesterone receptor B, estrogen receptor !, estrogen receptor”, and androgen receptor, has had a great impact, evident in the generation of several “knockout” mice for SRs. This review discusses the advances originating from the gene-targeting boom and the SR knockout mice. The broad content of this review is a reflection of the current state of research in female ovulation from these knockout female mice models.

Key Words:  ndrogen , estrogen , knockout female mouse , ovulation , progesterone , receptor , sex hormone

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References 

  1. Drummond AE , Britt KL , Dyson M , et al.   Ovarian steroid receptors and their role in ovarian function . Mol Cell Endocrinol . 2002;191:27–33
  2. Dorrington JH , Moon YS , Armstrong DT . Estradiol-17, biosynthesis in cultured granulosa cells from hypophysectomized immature rats; stimulation by follicle-stimulating hormone . Endocrinology . 1975;97:1328–1331
  3. Hillier SG , Tetsuka M . Role of androgens in follicle maturation and atresia . Baillieres Clin Obstet Gynaecol . 1997;11:249–260
  4. Mangelsdorf DJ , Thummel C , Beato M , et al.   The nuclear receptor superfamily: the second decade . Cell . 1995;83:835–839
  5. Wang PH , Chang C . Androgens and ovarian cancers . Eur J Gynecol Oncol . 2004;29:157–163
  6. Chang C , Saltzman A , Yeh S , et al.   Androgen receptor: an overview . Crit Rev Eukaryot Gene Expr . 1995;5:97–125
  7. Simoncini T , Genazzani AR . Non-genomic actions of sex steroid hormones . Eur J Endocrinol . 2003;148:281–292
  8. Heinlein CA , Chang C . Androgen receptor (AR) coregulators: an overview . Endocr Rev . 2002;23:175–200
  9. Szego CM , Pietras RJ . Subcellular distribution of oestrogen receptors . Nature . 1985;317:88–89
  10. Pietras RJ , Szego CM . Cell membrane estrogen receptors resurface . Nat Med . 1999;5:1330
  11. Heinlein CA , Chang C . The roles of androgen receptors and androgen-binding proteins in nongenomic androgen actions . Mol Endocrinol . 2002;16:2181–2187
  12. Couse JF , Korach KS . Estrogen receptor null mice: what have we learned and where will they lead us? . Endocr Rev . 1999;20:358–417
  13. Vanderhyden BC , Macdonald EA . Mouse oocytes regulate granulosa cell steroidogenesis throughout follicular development . Biol Reprod . 1998;59:1296–1301
  14. Vanderhyden BC , Tonary AM . Differential regulation of progesterone and estradiol production by mouse cumulus and mural granulosa cells by A factor(s) secreted by the oocyte . Biol Reprod . 1995;53:1243–1250
  15. Tetsuka M , Hillier SG . Differential regulation of aromatase and androgen receptor in granulosa cells . J Steroid Biochem Mol Biol . 1997;61:233–239
  16. Chang CS , Kokontis J , Liao ST . Molecular cloning of human and rat complementary DNA encoding androgen receptors . Science . 1988;240:324–326
  17. Chang CS , Kokontis J , Liao ST . Structural analysis of complementary DNA and amino acid sequences of human and rat androgen receptors . Proc Natl Acad Sci USA . 1988;85:7211–7215
  18. Yeh S , Tsai MY , Xu Q , et al.   Generation and characterization of androgen receptor knockout (ARKO) mice: an in vivo model for the study of androgen functions in selective tissues . Proc Natl Acad Sci USA . 2002;99:13498–13503
  19. O'Shaughnessy PJ , Johnston H , Willerton L , Baker PJ . Failure of normal adult Leydig cell development in androgen-receptor-deficient mice . J Cell Sci . 2002;115:3491–3496
  20. De Gendt K , Swinnen JV , Saunders PT , et al.   A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis . Proc Natl Acad Sci USA . 2004;101:1327–1332
  21. Collins LL, Lee HJ, Chen YT, Chang M, Hsu HY, Yeh S, et al. The androgen receptor in spermatogenesis . Cytogenet Genome Res . 2003;103:299–301
  22. Chang C , Chen YT , Yeh SD , et al.   Infertility with defective spermatogenesis and hypotestosteronemia in male mice lacking the androgen receptor in Sertoli cells . Proc Natl Acad Sci USA . 2004;101:6876–6881
  23. Lyon MF , Glenister PH . Reduced reproductive performance in androgen-resistant Tfm/Tfm female mice . Proc R Soc Lond B Biol Sci . 1980;208:1–12
  24. Lee DK , Chang C . Molecular communication between androgen receptor and general transcription machinery . J Steroid Biochem Mol Biol . 2003;84:41–49
  25. Heinlein CA , Chang C . Role of chaperones in nuclear translocation and transactivation of steroid receptors . Endocrine . 2001;14:143–149
  26. Daniel SA , Armstrong DT . Enhancement of follicle-stimulating hormone-induced aromatase activity by androgens in cultured rat granulosa cells . Endocrinology . 1980;107:1027–1033
  27. Vendola K , Zhou J , Wang J , Bondy CA . Androgens promote insulin-like growth factor-I and insulin-like growth factor-I receptor gene expression in the primate ovary . Hum Reprod . 1999;14:2328–2332
  28. Vendola KA , Zhou J , Adesanya OO , Weil SJ , Bondy CA . Androgens stimulate early stages of follicular growth in the primate ovary . J Clin Invest . 1998;101:2622–2629
  29. Billig H , Furuta I , Hsueh AJ . Estrogens inhibit and androgens enhance ovarian granulosa cell apoptosis . Endocrinology . 1993;133:2204–2222
  30. Hsueh AJ , Billig H , Tsafriri A . Ovarian follicle atresia: a hormonally controlled apoptotic process . Endocr Rev . 1994;15:707–724
  31. Cheng G , Weihua Z , Makinen S , et al.   A role for the androgen receptor in follicular atresia of estrogen receptor beta knockout mouse ovary . Biol Reprod . 2002;66:77–84
  32. Sato T , Matsumoto T , Yamada T , Watanabe T , Kawano H , Kato S . Late onset of obesity in male androgen receptor-deficient (AR KO) mice . Biochem Biophys Res Commun . 2003;300:167–171
  33. Yeh S , Hu YC , Wang PH , et al.   Abnormal mammary gland development and growth retardation in female mice and MCF7 breast cancer cells lacking androgen receptor . J Exp Med . 2003;198:1899–1908
  34. Hu YC , Wang PH , Yeh S , et al.   Subfertility and defective folliculogenesis in female mice lacking androgen receptor . Proc Natl Acad Sci USA . 2004;101:11209–11214
  35. Allen E , Doisy EA . An ovarian hormone. Preliminary report on its localization, extraction and partial purification, and action in test animals . JAMA . 1923;81:819–821
  36. Rosenfeld CS , Wagner JS , Roberts RM , Lubahn DB . Intraovarian actions of oestrogen . Reproduction . 2001;122:215–226
  37. Fisher CR , Graves KH , Parlow AF , Simpson ER . Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cyp19 gene . Proc Natl Acad Sci USA . 1998;95:6965–6970
  38. Honda S , Harada N , Ito S , Takagi Y , Maeda S . Disruption of sexual behavior in male aromatase-deficient mice lacking exons 1 and 2 of the cyp19 gene . Biochem Biophys Res Commun . 1998;252:445–449
  39. Lubahn DB , Moyer JS , Golding TS , Couse JF , Korach KS , Smithies O . Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene . Proc Natl Acad Sci USA . 1993;90:11162–11166
  40. Krege JH , Hodgin JB , Couse JF , et al.   Generation and reproductive phenotypes of mice lacking estrogen receptor beta . Proc Natl Acad Sci USA . 1998;95:15677–15682
  41. Couse JF, Hewitt SC, Bunch DO, Sar M, Walker VR, Davis BJ, et al. Postnatal sex reversal of the ovaries in mice lacking estrogen receptors alpha and beta . Science . 1999;286:2328–2331
  42. Dupont S , Krust A , Gansmuller A , Dierich A , Chambon P , Mark M . Effect of single and compound knockouts of estrogen receptors alpha (ERalpha) and beta (ERbeta) on mouse reproductive phenotypes . Development . 2000;127:4277–4291
  43. Green S, Walter P, Kumar V, Krust A, Bornert JM, Argos P, et al. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A . Nature . 1986;320:134–139
  44. Greene GL , Gilna P , Waterfield M , Baker A , Hort Y , Shine J . Sequence and expression of human estrogen receptor complementary DNA . Science . 1986;231:1150–1154
  45. Kuiper GG , Enmark E , Pelto-Huikko M , Nilsson S , Gustafsson JA . Cloning of a novel receptor expressed in rat prostate and ovary . Proc Natl Acad Sci USA . 1996;93:5925–5930
  46. Mosselman S , Polman J , Dijkema R . ER beta: identification and characterization of a novel human estrogen receptor . FEBS Lett . 1996;392:49–53
  47. Sharma SC , Clemens JW , Pisarska MD , Richards JS . Expression and function of estrogen receptor subtypes in granulosa cells: regulation by estradiol and forskolin . Endocrinology . 1999;140:4320–4334
  48. Schomberg DW, Couse JF, Mukherjee A, Lubahn DB, Sar M, Mayo KE, et al. Targeted disruption of the estrogen receptor-alpha gene in female mice: characterization of ovarian responses and phenotype in the adult . Endocrinology . 1999;140:2733–2744
  49. Couse JF , Curtis Hewitt S , Korach KS . Receptor null mice reveal contrasting roles for estrogen receptor alpha and beta in reproductive tissues . J Steroid Biochem Mol Biol . 2000;74:287–296
  50. Couse JF , Korach KS . Contrasting phenotypes in reproductive tissues of female estrogen receptor null mice . Ann NY Acad Sci . 2001;948:1–8
  51. Adler S , Waterman ML , He X , Rosenfeld MG . Steroid receptor-mediated inhibition of rat prolactin gene expression does not require the receptor DNA-binding domain . Cell . 1988;52:685–695
  52. Feng W , Ribeiro RC , Wagner RL , et al.   Hormone-dependent coactivator binding to a hydrophobic cleft on nuclear receptors . Science . 1998;280:1747–1749
  53. Ignar-Trowbridge DM, Nelson KG, Bidwell MC, Curtis SW, Washburn TF, McLachlan JA, et al. Coupling of dual signaling pathways: epidermal growth factor action involves the estrogen receptor . Proc Natl Acad Sci USA . 1992;89:4658–4662
  54. Richards JS , Ireland JJ , Rao MC , Bernath GA , Midgley AR , Reichert LE . Ovarian follicular development in the rat: hormone receptor regulation by estradiol, follicle stimulating hormone and luteinizing hormone . Endocrinology . 1976;99:1562–1570
  55. Richards JS . Perspective: the ovarian follicle – a perspective in 2001 . Endocrinology . 2001;142:2184–2193
  56. Britt KL , Findlay JK . Regulation of the phenotype of ovarian somatic cells by estrogen . Mol Cell Endocrinol . 2003;202:11–17
  57. Nielsen M , Bjornsdottir S , Hoyer PE , Byskov AG . Ontogeny of oestrogen receptor alpha in gonads and sex ducts of fetal and newborn mice . J Reprod Fertil . 2000;118:195–204
  58. Mowa CN , Iwanaga T . Differential distribution of oestrogen receptor-alpha and -beta mRNAs in the female reproductive organ of rats as revealed by in situ hybridization . J Endocrinol . 2000;165:59–66
  59. Jefferson WN , Couse JF , Banks EP , Korach KS , Newbold RR . Expression of estrogen receptor beta is developmentally regulated in reproductive tissues of male and female mice . Biol Reprod . 2000;62:310–317
  60. Byers M , Kuiper GG , Gustafsson JA , Park-Sarge OK . Estrogen receptor-beta mRNA expression in rat ovary: downregulation by gonadotropins . Mol Endocrinol . 1997;11:172–182
  61. Britt KL , Findlay JK . Estrogen actions in the ovary revisited . J Endocrinol . 2002;175:269–276
  62. Hirshfield AN . Development of follicles in the mammalian ovary . Int Rev Cytology . 1991;124:43–101
  63. Taketo T . Production of mullerian-inhibiting substance (MIS) and sulfated glycoprotein-2 (SGP-2) associated with testicular differentiation in the XX mouse gonadal graft . Ann NY Acad Sci . 1991;637:74–89
  64. Morais da Silva S , Hacker A , Harley V , Goodfellow P , Swain A , Lovell-Badge R . Sox9 expression during gonadal development implies a conserved role for the gene in testis differentiation in mammals and birds . Nat Genet . 1996;14:62–68
  65. Mulac-Jericevic B , Conneely OM . Reproductive tissue selective actions of progesterone receptors . Reproduction . 2004;128:139–146
  66. Conneely OM , Mulac-Jericevic B , DeMayo F , Lydon JP , O'Malley BW . Reproductive functions of progesterone receptors . Recent Prog Horm Res . 2002;57:339–355
  67. Tsai MJ , O'Malley BW . Molecular mechanisms of action of steroid/thyroid receptor superfamily members . Annu Rev Biochem . 1994;63:451–456
  68. Graham JD , Clarke CL . Physiological action of progesterone in target tissues . Endocr Rev . 1997;18:502–519
  69. Conneely OM , Kettelberger DM , Tsai MJ , Schrader WT , O'Malley BW . The chicken progesterone receptor A and B isoforms are products of an alternate translation initiation event . J Biol Chem . 1989;264:14062–14064
  70. Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H, et al. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B . EMBO J . 1990;9:1847–1857
  71. Shyamala G , Schneider W , Schott D . Developmental regulation of murine mammary progesterone receptor gene expression . Endocrinology . 1990;126:2882–2889
  72. Duffy DM , Wells TR , Haluska GJ , Stouffer RL . The ratio of progesterone receptor isoforms changes in the monkey corpus luteum during the luteal phase of the menstrual cycle . Biol Reprod . 1997;57:693–699
  73. Graham JD, Yeates C, Balleine RL, Harvey SS, Milliken JS, Bilous AM, et al. Progesterone receptor A and B protein expression in human breast cancer . J Steroid Biochem Mol Biol . 1996;56:93–98
  74. Guiochon-Mantel A , Loosfelt H , Lescop P . Mechanisms of nuclear localization of the progesterone receptor: evidence for interaction between monomers . Cell . 1989;57:1147–1154
  75. Rowan BG , O'Malley BW . Progesterone receptor coactivators . Steroids . 2000;65:545–549
  76. Sartorius CA , Melville MY , Hovland AR , Tung L , Takimoto GS , Horwitz KB . A third transactivation function (AF3) of human progesterone receptors located in the unique N- terminal segment of the B-isoform . Mol Endocrinol . 1994;8:1347–1360
  77. Giangrande PH , Kimbrel EA , Edwards DP , McDonnell DP . The opposing transcriptional activities of the two isoforms of the human progesterone receptor are due to differential cofactor binding . Mol Cell Biol . 2000;20:3102–3115
  78. Tora L , Gronemeyer H , Turcotte B , Gaub MP , Chambon P . The N-terminal region of the chicken progesterone receptor specifies target gene activation . Nature . 1988;333:185–188
  79. McDonnell DP , Shahbaz MM , Vegeto E , Goldman ME . The human progesterone receptor A-form functions as a transcriptional modulator of mineralocortocoid receptor transcriptional activity . J Steroid Biochem Mol Biol . 1994;48:425–432
  80. Giangrande PH , McDonnell DP . The A and B isoforms of the human progesterone receptor: two functionally different transcription factors encoded by a single gene . Recent Prog Horm Res . 1999;54:291–313
  81. Loutradis D , Bletsa R , Aravantinos L , Kallianidis K , Michalas S , Psychotos A . Preovulatory effects of the progesterone antagonist mifepristone (RU486) in mice . Hum Reprod . 1991;6:1238–1240
  82. Lydon JP , DeMayo FJ , Funk CR , et al.   Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities . Genes Dev . 1995;9:2266–2278
  83. Chappell PE , Lydon JP , Conneely OM , O'Malley BW , Levine JE . Endocrine defects in mice carrying a null mutation for the progesterone receptor gene . Endocrinology . 1997;138:4147–4152
  84. Mulac-Jericevic B , Mullinax RA , DeMayo F , Lydon JP , Conneely OM . Subgroup of reproductive functions of progesterone mediated by progesterone receptor-B isoform . Science . 2000;289:1751–1754
  85. Robker RL , Russell DL , Espey LL , Lydon JP , O'Malley BW , Richards JS . Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases . Proc Natl Acad Sci USA . 2000;97:4689–4694
  86. Robker RL , Russell DL , Yoshioka S , et al.   Ovulation: a multigene, multi-step process . Steroids . 2000;65:559–570
  87. Natraj U , Richards JS . Hormonal regulation, localization, and functional activity of the progesterone receptor in granulosa cells of rat preovulatory follicles . Endocrinology . 1993;133:761–769

PII: S1028-4559(09)60101-7

doi:10.1016/S1028-4559(09)60101-7

Taiwanese Journal of Obstetrics and Gynecology
Volume 44, Issue 1 , Pages 16-25, March 2005

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