Regulation of Ovarian Inhibin and Activin Gene Expression by Gonadotropins

  • Robin E. Dodson
  • Lin Pei
  • Ok-Kyong Park
  • Joanna C. Dykema
  • Kelly E. Mayo
Part of the Serono Symposia USA book series (SERONOSYMP)


Follicle stimulating hormone (FSH) plays a critical role in regulating ovarian function and is a key hormone in initiating follicular recruitment and promoting follicular maturation (1). Additionally, it influences differentiation by modulating steroidogenesis, inducing luteinizing hormone receptors and regulating the synthesis of ovarian hormones, such as inhibin and activin. Inhibin is an important regulator of FSH synthesis and secretion in rats (2), while activin appears to be a paracrine regulator of ovarian function (3, 4) that may also be involved in FSH regulation (5, 6). The study of how these two genes are regulated is important for understanding aspects of the reproductive cycle. This report focuses on the regulation of inhibin and activin gene expression in rat granulosa cells (GC) by gonadotropins.


Granulosa Cell Follicle Stimulate Hormone Follicular Fluid Luteinizing Hormone Receptor Chloramphenicol Acetyl Transferase 
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  1. 1.
    Dorrington J, Armstrong D. Effects of FSH on gonadal functions. Recent Prog Horm Res 1979; 35: 1–42.Google Scholar
  2. 2.
    De Jong FH. Inhibin. Physiol Rev 1988; 68: 555–607.PubMedGoogle Scholar
  3. 3.
    Hsueh AJW, Dahl KD, Vaughan J, et al. Heterodimers and homodimers of inhibin subunits have different paracrine action in the modulation of luteinizing hormone-stimulated androgen biosynthesis. Proc Nail Acad Sci USA 1987; 84: 5082–6.CrossRefGoogle Scholar
  4. 4.
    LaPolt PS, Soto D, Su J-G, et al. Activin stimulation of inhibin secretion and messenger RNA levels in cultured granulosa cells. Mol Cell Endocrinol 1989; 3: 1666–73.CrossRefGoogle Scholar
  5. 5.
    Ling N, Ying S-Y, Ueno N, et al. Pituitary FSH is released by a heterodimer of the fi-subunits from the two forms of inhibin. Nature 1986; 321: 779–82.PubMedCrossRefGoogle Scholar
  6. 6.
    Vale W, Rivier J, Vaughan J, et al. Purification and characterization of an FSHreleasing protein from porcine ovarian follicular fluid. Nature 1986; 321: 779–82.CrossRefGoogle Scholar
  7. 7.
    Robertson DM, Foulds LM, Leversha L, et al. Isolation of inhibin from bovine follicular fluid. Biochem Biophys Res Commun 1985; 126: 220–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Miyamoto K, Hasegawa Y, Fukuda M, et al. Isolation of porcine follicular fluid inhibin of about 32 kDa. Biochem Biophys Res Commun 1985; 129: 396–403.PubMedCrossRefGoogle Scholar
  9. 9.
    Ling N, Ying S-Y, Ueno N, Esch F, Denoroy L, Guillemin R. Isolation and partial characterization of a Mr 32,000 protein with inhibin activity from porcine ovarian follicular fluid. Proc Natl Acad Sci USA 1985; 82: 7217–21.PubMedCrossRefGoogle Scholar
  10. 10.
    Rivier J, Spiess J, McClintock R, Vaughan J, Vale W. Purification and partial characterization of inhibin from porcine follicular fluid. Biochem Biophys Res Commun 1985; 133: 120–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Bicsak TA, Tucker EM, Cappel S, et al. Hormonal regulation of granulosa cell inhibin biosynthesis. Endocrinology 1986; 119: 2711–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Merchenthaler I, Culler MK, Petrusz P, Negro-Villar A. Immunocytochemical localization of inhibin in rat and human reproductive tissues. Mol Cell Endocrinol 1987; 54: 236–43.CrossRefGoogle Scholar
  13. 13.
    Cuevas P, Ying S-Y, Ling N, Ueno N, Esch F, Guillemin R. Immunohistochemical detection of inhibin on the gonads. Biochem Biophys Res Commun 1987; 142: 23–30.PubMedCrossRefGoogle Scholar
  14. 14.
    Woodruff TK, Meunier H, Jones PBC, Hsueh AJW, Mayo KE. Rat inhibin: molecular cloning of a-and O-subunit complementary deoxyribonucleic acids and expression in the ovary. Mol Cell Endocrinol 1987; 1: 561–8.CrossRefGoogle Scholar
  15. 15.
    Woodruff TK, D’Agostino J, Schwartz NB, Mayo KE. Dynamic changes in inhibin messenger RNAs in rat ovarian follicles during the reproductive cycle. Science 1988; 239: 1296–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Meunier H, Cajander SB, Roberts VJ, et al. Rapid changes in the expression of inhibin a-, PA-, and (3B-subunits in ovarian cell types during the rat estrous cycle. Mol Cell Endocrinol 1988; 2: 1352–63.CrossRefGoogle Scholar
  17. 17.
    Lee VWK, McMaster J, Quigg H, Findlay J, Leversha L. Ovarian and peripheral blood inhibin concentration increase with gonadotropin treatment in immature rats. Endocrinology 1981; 108: 2403–5.PubMedCrossRefGoogle Scholar
  18. 18.
    Meunier H, Roberts VJ, Sawchenko PE, Cajander SB, Hseuh AJW, Vale W. Periovulatory changes in the expression of inhibin a-, PA-, PB-subunits in hormonally induced immature female rats. Mol Cell Endocrinol 1989; 3: 2062–9.CrossRefGoogle Scholar
  19. 19.
    Davis SR, Burger HG, Robertson DM, Farnworth PG, Carson RS, Krozowski Z. Pregnant mare’s serum gonadotropin stimulates inhibin subunit gene expression in the immature rat ovary: dose response characteristics and relationships to serum gonadotropins, inhibin and ovarian steroid content. Endocrinology 1988; 123: 2399–407.PubMedCrossRefGoogle Scholar
  20. 20.
    Rivier C, Roberts V, Vale W. Possible role of luteinizing hormone and follicle-stimulating hormone in modulating inhibin secretion and expression during the estrous cycle of the rat. Endocrinology 1989; 125: 876–82.PubMedCrossRefGoogle Scholar
  21. 21.
    Woodruff TK, D’Agostino J, Schwartz NB, Mayo KE. Decreased inhibin gene expression in preovulatory follicles requires primary gonadotropin surges. Endocrinology 1989; 124: 2193–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Krummen LA, Toppari J, Kim WH, et al. Regulation of testicular inhibin subunit messenger ribonucleic acid levels in vivo: effects of hypophysectomy and selective follicle-stimulating hormone replacement. Endocrinology 1989; 125: 1630.PubMedCrossRefGoogle Scholar
  23. 23.
    Feng Z-M, Bardin CW, Chen C-LC. Characterization and regulation of testicular inhibin 3-subunit mRNA. Mol Cell Endocrinol 1989; 3: 939–48.CrossRefGoogle Scholar
  24. 24.
    Bardin CW, Morris PL, Shaha C, et al. Inhibin structure and function in the testis. Ann NY Acad Sci 1989; 565: 10–23.CrossRefGoogle Scholar
  25. 25.
    Schwall RH, Mason AJ, Wilcox JM, Bassett SC, Zeleznik AJ. Localization of inhibin activin subunit messenger RNAs within the primate ovary. Mol Cell Endocrinol 1990; 4: 75–9.CrossRefGoogle Scholar
  26. 26.
    Feng Z-M, Li Y-P, Chen C-LC. Analysis of the 5’-flanking regions of rat inhibin a-and PB-subunit genes suggests two different regulatory mechanisms. Mol Cell Endocrinol 1989; 3: 1914–25.CrossRefGoogle Scholar
  27. 27.
    Suhr ST, Rahal JO, Mayo KM. Mouse growth hormone-releasing hormone: precursor structure and expression in brain and placenta. Mol Cell Endocrinol 1989; 3: 1693–1700.CrossRefGoogle Scholar
  28. 28.
    Epstein-Almog R, Orly J. Inhibition of hormone-induced steroidogenesis during cell proliferation in serum-free cultures of rat granulosa cells. Endocrinology 1985; 116: 2103–12.Google Scholar
  29. 29.
    Feigner PL, Holm M. Cationic liposome-mediated transfection. Focus 1989; 11: 21–5.Google Scholar
  30. 30.
    Chen C, Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol 1987; 7: 2745–52.PubMedGoogle Scholar
  31. 31.
    Ackland JF, D’Agostino J, Ringstrom SJ, Hostetler JP, Mann BG, Schwartz NB. Circulating radioimmunoassayable inhibin during periods of transient follicle-stimulating hormone rise: secondary surge and unilateral ovariectomy. Biol Reprod 1990; 43: 347–52.PubMedCrossRefGoogle Scholar
  32. 32.
    Chomczynski P, Sacchi N. Single step method of RNA isolation by acid guanidium thiocyanate phenol-chloroform extraction. Anal Biochem 1987; 162: 156–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Gorman CM, Moffat LF, Howard BH. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol 1982; 2: 1044–51.PubMedGoogle Scholar
  34. 34.
    Wood WM, Kao MY, Gordon DF, Ridgway EC. Thyroid hormone regulates the mouse thyrotropin p-subunit gene promoter in transfected primary thyrotrophs. J Biol Chem 1989; 264: 14840–7.PubMedGoogle Scholar
  35. 35.
    Maxwell IH, Harrison GS, Wood WM, Maxwell F. A DNA cassette containing a trimerized SV40 polyadenylation signal which efficiently blocks spurious plasmid-initiated transcription. BioTechniques 1989; 7: 276–80.Google Scholar
  36. 36.
    Bicsak TA, Colander SB, Vale W, Hsueh AJW. Inhibin: studies of stored and secreted forms by biosynthetic labeling and immunodetection in cultured rat granulosa cells. Endocrinology 1988; 122: 741–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Suzuki T, Miyamoto K, Hasegawa Y, et al. Regulation of inhibin production by rat granulosa cells. Mol Cell Endocrinol 1987; 54: 185–95.PubMedCrossRefGoogle Scholar
  38. 38.
    Mang Z, Lee VWK, Carson RS, Burger HG. Selective control of rat granulosa cell inhibin production by FSH and LH in vitro. Mol Cell Endocrinol 1988; 56: 35–40.CrossRefGoogle Scholar
  39. 39.
    LaPolt PS, Piquette GN, Soto D, Sincich C, Hseuh AJW. Regulation of inhibin subunit messenger ribonucleic acid levels by gonadotropin, growth factors and gonadotropin-releasing hormone in cultured rat granulosa cells. Endocrinology 1990; 127: 823–31.PubMedCrossRefGoogle Scholar
  40. 40.
    Amsterdam A, Rotmensch S. Structure-function relationships during granulosa cell differentiation. Endocr Rev 1987; 8: 309–337.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 1992

Authors and Affiliations

  • Robin E. Dodson
  • Lin Pei
  • Ok-Kyong Park
  • Joanna C. Dykema
  • Kelly E. Mayo

There are no affiliations available

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