Advertisement

Regulation of Granulosa Cell Responsiveness to Gonadotropins: Actions of Epidermal and Platelet-Derived Growth Factors

  • Judith S. Mondschein
  • David W. Schomberg
Part of the Biochemical Endocrinology book series (BIOEND, volume 1)

Abstract

The concept of pituitary gonadotropins as regulators of follicular and luteal development and function is central to our understanding of ovarian physiology. Patterns of gonadotropin secretion are superimposed upon patterns of target cell gonadotropin receptor levels (Richards and Midgley, 1976). The result of this well-coordinated series of events is a normal estrus or menstrual cycle. Steroid hormones provide a second level of regulation of these processes. As early as 1940 it was observed that estrogen enhanced ovarian responsiveness to gonadotropins (Pencharz, 1940). More recent studies have suggested roles for estrogens , androgens, and progestins in various aspects of ovarian physiology and pathophysiology (McNatty et al., 1979; Louvet et al., 1975; Schomberg, 1979; Schreiber and Hsueh, 1979; and references therein). The observation that growth factors can modulate follicle-stimulating hormone (FSH)-dependent luteinizing hormone (LH) receptor induction in vitro (Mondschein and Schomberg, 1981a) introduced the possibility of a third level of regulation: the growth factors, known primarily for their mitogenic effects on cultured cells, may represent a broad class of compounds which interact with more classic gonadotropic and steroidal mechanisms to determine the course of follicular and luteal development and function.

Keywords

Epidermal Growth Factor Receptor Granulosa Cell Luteal Cell Leydig Tumor Cell Ovarian Granulosa Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Antoniades, H. N., Scher, C. D., and Stiles, C. D., 1979, Purification of human platelet-derived growth factor, Proc. Natl. Acad. Sci. USA 76:1809.PubMedCrossRefGoogle Scholar
  2. Ascoli, M., 1981, Regulation of gonadotropin receptors and gonadotropin responsiveness in a clonal strain of Leydig tumor cells by epidermal growth factor, J. Biol. Chem. 256:179.PubMedGoogle Scholar
  3. Byyny, R. L., Orth, D. N., Cohen, S., and Doyne, E. S., 1974, Epidermal growth factor: effects of androgens and adrenergic agents, Endocrinology 95:776.PubMedCrossRefGoogle Scholar
  4. Carpenter, G., and Cohen, S., 1976, 125I-labeled human epidermal growth factor: binding, internalization, and degradation in human fibroblasts, J. Cell Biol. 79:159.CrossRefGoogle Scholar
  5. Channing, C. P., 1969, The use of tissue culture of granulosa cells as a method of studying the mechanism of luteinization, in: “The Gonads”, K. W. McKerns, ed., pp. 245–275, Appleton-Century Crofts, New York.Google Scholar
  6. Deuel, T. F., Huang, J. S., Proffitt, R. T., Baenziger, J. U., Chang, D., and Kennedy, B. B., 1981, Human platelet-derived growth factor: purification and resolution into two active protein fractions, J. Biol. Chem. 256:8896.PubMedGoogle Scholar
  7. Erickson, G. F., and Case, E., 1982, Epidermal growth factor inhibits LH-dependent theca/interstitial cell differentiation in serum-free culture, Endocrinology 110 (Supplement): 237 (Abstract #773).Google Scholar
  8. Erickson, G. F., Wang, C., and Hsueh, A. J. W., 1979, FSH induction of functional LH receptors in granulosa cells cultured in chemically defined medium, Nature 279:336.PubMedCrossRefGoogle Scholar
  9. Erickson, G. F., Wang, C., and Casper, R., 1982, Studies on the mechanism of LH receptor control by FSH, Proceedings of the 29th Annual Meeting of the Society for Gynecological Investigation, Abstract #281, p. 162.Google Scholar
  10. Erwin, B. G., Stoschek, C. M., and Florini, J. R., 1981, A rapid fluorometric method for the estimation of DNA in cultured cells, Anal. Biochem. 110:291.PubMedCrossRefGoogle Scholar
  11. Garrett, R., Kroman, N., Conn, T., and Channing, C. P., 1983, Ability of EGF and FGF to enhance growth of porcine granulosa cells in culture while they lead to a decrease in progesterone secretion: changes in responsiveness throughout follicular maturation, in: “Factors Regulating Ovarian Function”, P. Terranova and G. S. Greenwald, eds., Raven Press, New York. (In press.)Google Scholar
  12. Gospodarowicz, D., and Bialecki, H., 1979, Fibroblast and epidermal growth factors are mitogenic agents for cultured granulosa cells of rodent, porcine, and human origin, Endocrinology 104:757.PubMedCrossRefGoogle Scholar
  13. Gospodarowicz, D., Mescher, A. L., and Birdwell, C. R., 1978a, Control of cellular proliferation by the fibroblast and epidermal growth factors, Natl. Cancer Inst. Monogr. 48:109.PubMedGoogle Scholar
  14. Gospodarowicz, D., Vlodavsky, I., Bialecki, H., and Brown, K. D., 1978b, The control of proliferation of ovarian cells by the epidermal and fibroblast growth factors, in: “Novel Aspects of Reproductive Physiology”, C. H. Spilman and J. W. Wilks, eds., pp. 107–108, Spectrum Publications, New York.Google Scholar
  15. Heldin, C.-H., Wasteson, A., and Westermark, B., 1981, Specific binding of 125I-labeled platelet-derived growth factor to cultured cells, in: “The Biology of Normal Human Growth”, M. Ritzen, ed., pp. 23–31, Raven Press, New York.Google Scholar
  16. Hseuh, A. J. W., and Erickson, G. F., 1979, Extrapituitary action of gonadotropin-releasing hormone: direct inhibition of ovarian steroidogenesis, Science, 204:854.CrossRefGoogle Scholar
  17. Hsueh, A. J. W., and Ling, N. C., 1979, Effect of an antagonistic analog of gonadotropin-releasing hormone upon ovarian granulosa cell function, Life Sci. 25:1223.PubMedCrossRefGoogle Scholar
  18. Hsueh, A. J. W., and Jones, P. B. C., 1982, Direct hormonal modulation of ovarian granulosa cell maturation: effect of gonadotropin-releasing hormone, in: “Follicular Maturation and Ovulation”, International Congress Series #506, R. Roland, E. V. Van Hall, S. G., Hillier, K. P., McNatty, and J. Schoemaker, eds., pp. 19–33, Exerpta Medica, Amsterdam.Google Scholar
  19. Hsueh, A. J. W., Welsh, T. H., and Jones, P. B. C., 1981, Inhibition of ovarian and testicular steroidogenesis by epidermal growth factor, Endocrinology 108:2002.PubMedCrossRefGoogle Scholar
  20. Johnson, L. K., Baxter, J. D., Vlodavsky, I., and Gospodarowicz, D., 1980, Epidermal growth factor and expression of specific genes: effects on cultured rat pituitary cells are dissociable from the mitogenic response, Proc. Natl. Acad. Sci. USA 77:394.PubMedCrossRefGoogle Scholar
  21. Jones, P. B. C., and Hsueh, A. J. W., 1981, Regulation of ovarian 2Oa-hydroxysteroid dehydrogenase by gonadotropinreleasing hormone and its antagonist in vitro and in vivo, J. Steroid Biochem. 14:1169.PubMedCrossRefGoogle Scholar
  22. Jones, P. B. C., Conn, P. M., Marian, J., and Hsueh, A. J. W., 1980, Binding of gonadotropin-releasing hormone agonist to rat ovarian granulosa cells, Life Sci. 27:2125.PubMedCrossRefGoogle Scholar
  23. Jones, P. B. C., Welsh, T. H., and Hsueh, A. J. W., 1983, Regulation of ovarian progestin production by epidermal growth factor in cultured granulosa cells, in: “Factors Regulating Ovarian Function”, P. Terranova and G. S. Greenwald, eds., Raven Press, New York (in press).Google Scholar
  24. Knecht, M., and Catt, K. J., 1981, Gonadotropin-releasing hormone: regulation of adenosine 3’,5’-monophosphate in ovarian granulosa cells, Science 214:1346.PubMedCrossRefGoogle Scholar
  25. Knecht, M., and Ranta, T., 1982, Growth factors modify granulosa cell function through alterations in FSH-induced cAMP accumulation, Endocrinology 110 (Supplement):290 (Abstract #841).CrossRefGoogle Scholar
  26. Knecht, M., Amsterdam, A., and Catt, K. J., 1981, The regulatory role of cAMP in hormone-induced granulosa cell differentiation, J. Biol. Chem. 256:10628.PubMedGoogle Scholar
  27. Louvet, J.-P., Harman, S. M., Schreiber, J. R., and Ross, G. T., 1975, Evidence for a role of androgens in follicular maturation, Endocrinology 97:366.PubMedCrossRefGoogle Scholar
  28. McNatty, K. P., Smith, D. M., Makris, A., Osathanondh, R., and Ryan, K., 1979, The microenvironment of the human antral follicle: interrelationships among steroid levels in antral fluid, the population of granulosa cells, and the status of the oocyte in vivo and in vitro, J. Clin. Endocrinol. Metab. 49:851.PubMedCrossRefGoogle Scholar
  29. Mondschein, J. S., and Schomberg, D. W., 1981a, Growth factors modulate gonadotropin receptor induction in granulosa cell cultures, Science 211:1179.PubMedCrossRefGoogle Scholar
  30. Mondschein, J. S., and Schomberg, D. W., 1981b, Platelet-derived growth factor enhances granulosa cell luteinizing hormone receptor induction by follicle-stimulating hormone and serum, Endocrinology 109:325.PubMedCrossRefGoogle Scholar
  31. Mondschein, J. S., May, J. V., Gunn, E. B., and Schomberg, D. W., 1981, Modulation by epidermal growth factor of LH/hCG receptor binding in porcine granulosa cell cultures: implications for follicle development and atresia, in: “Dynamics of Ovarian Function”, N. B. Schwartz and M. Hunzicker-Dunn, eds., pp. 83–88, Raven Press, New York.Google Scholar
  32. Nimrod, A., 1981, The induction of ovarian LH-receptors by FSH is mediated by cAMP, F. E. B. S. Letters 131:31.CrossRefGoogle Scholar
  33. Nimrod, A., and Lindner, H. R., 1976, A synergistic effect of androgen on the stimulation of progesterone secretion by FSH in cultured rat granulosa cells, Mol. Cell. Endocrinol. 5:315.PubMedCrossRefGoogle Scholar
  34. Pencharz, R. I., 1940, Effects of estrogen and androgens alone and in combination with chorionic gonadotropin on the ovary of the hypophysectomized rat, Science 91:554.PubMedCrossRefGoogle Scholar
  35. Rao, M. C., Richards, J. S., and Midgley, A. R., Jr., 1977, Regulation of gonadotropin receptors by luteinizing hormone in granulosa cells, Endocrinology 101:512.PubMedCrossRefGoogle Scholar
  36. Reichert, L. E., Jr., Sanzo, M. A., and Darga, N. S., 1979, Studies on a low molecular weight follicle-stimulating hormone binding inhibitor from human serum, J. Clin. Endocrinol. Metab. 49:866.PubMedCrossRefGoogle Scholar
  37. Richards, J. S., 1980, Maturation of ovarian follicles: actions and interactions of pituitary and ovarian hormones on follicular cell differentiation, Physiol. Rev. 60:51.PubMedGoogle Scholar
  38. Richards, J. S., and Midgley, A. R., Jr., 1976, Protein hormone action: a key to understanding ovarian follicular and luteal cell development, Biol. Reprod. 14:1562.CrossRefGoogle Scholar
  39. Richards, J. S., Ireland, J. J., Rao, M. C., Bernath, G. A., Midgley, A. R., Jr., and Reichert, L. E., Jr., 1976, Ovarian follicular development in the rat: hormone receptor regulation by estradiol, follicle-stimulating hormone, and luteinizing hormone, Endocrinology 99:1563.Google Scholar
  40. Ross, R., 1981, The platelet-derived growth factor, in: “Tissue Growth Factors”, R. Baserga, ed., pp. 133–159, SpringerVerlag, Berlin.CrossRefGoogle Scholar
  41. Sanders, M. M., and Midgley, A. R., Jr., 1981, Cyclic nucleo-tides can induce LH/hCG receptors in cultured rat granulosa cells, Endocrinology 108 (Supplement):165 (Abstract #332).Google Scholar
  42. Schomberg, D. W., 1979, Steroidal modulation of steroid secretion in vitro: an experimental approach to intra-follicular regulation mechanisms, in: “Ovarian Follicular and Corpus Luteum Function”, C. P. Channing, J. M. Marsh, and W. A. Sadler, eds., pp. 155–168, Plenum Press, New York.Google Scholar
  43. Schomberg, D. W., Stouffer, R. L., and Tyrey, L., 1976, Modulation of progestin secretion in ovarian cells by 17β-hydroxy-5α-androstan-3-one (dihydrotestosterone): a direct demonstration in monolayer culture, Biochem. Biophys. Res. Comm. 68:77.PubMedCrossRefGoogle Scholar
  44. Schomberg, D. W., May, J. V., and Mondschein, J. S., 1983a, Epidermal growth factor attenuates FSH-, cAMP-, or cholera toxin-mediated LH receptor induction in granulosa cell cultures, in: “Factors Regulating Ovarian Function”, P. Terranova and G. S. Greenwald, eds., Raven Press, New York (in press).Google Scholar
  45. Schomberg, D. W., May, J. V., and Mondschein, J. S., 1983b, Interactions between hormones and growth factors in the regulation of granulosa cell differentiation in vitro, J. Steroid Biochem. (in press).Google Scholar
  46. Schreiber, J. R., and Hsueh, A. J. W., 1979, Progesterone “receptor” in rat ovary, Endocrinology 105:915.PubMedCrossRefGoogle Scholar
  47. St-Arnaud, R., Kelly, P. A., Walker, P., and Labrie, F., 1983, Characterization and hormonal control of epidermal growth factor (EGF) receptors in the rat ovary, in: “Factors Regulating Ovarian Function”, P. Terranova and G. S. Greenwald, eds., Raven Press, New York (in press).Google Scholar
  48. Vlodavsky, I., Brown, K. D., and Gospodarowicz, D., 1978, A comparison of the binding of epidermal growth factor to cultured granulosa and luteal cells, J. Biol. Chem. 253:3744.PubMedGoogle Scholar
  49. Zeleznik, A. J., Midgley, A. R., Jr., and Reichert, L. E., 1974, Granulosa cell maturation in the rat: increased binding of hCG following treatment with FSH in vivo, Endocrinology 95:818.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Judith S. Mondschein
    • 1
  • David W. Schomberg
    • 1
  1. 1.Departments of Obstetrics and Gynecology and PhysiologyDuke University Medical CenterDurhamUSA

Personalised recommendations