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Regulation of the LH/CG Receptor by Gonadotropins

  • Deborah L. Segaloff
  • JoAnne S. Richards
  • Mario Ascoli
  • Haiyun Wang
Part of the Serono Symposia USA book series (SERONOSYMP)

Abstract

The induction of the lutropin/choriogonadotropin receptor (LH/CG-R) by follicle-stimulating hormone (FSH) is one of the hallmarks of the differentiating granulosa cell (GC) (1–3). The mechanisms underlying the induction and regulation of the LH/CG-R, however, are for the most part not well understood. Utilizing cultured GC, many different laboratories have characterized the FSH-dependent induction of LH/CG-R as defined by hCG binding activity. From these experiments, it has been possible to make the following conclusions. (1) The induction of the LH/CG-R by FSH is mediated by the FSH-induced increase in intracellular cAMP (4–7). Thus, other agents that increase intracellular cAMP, such as cholera toxin, forskolin, or exogenously added cAMP derivatives, are capable of mimicking the induction of the LH/CG-R. (2) The dose-response curve for the induction of the LH/CG-R by FSH or agents that increase cAMP is bell shaped, such that at high concentrations of hormone or cAMP, the induction is submaximal (5, 8, 9). (3) The time course of this induction process is relatively slow, with increased hCG binding activity in cells cultured with FSH observed only 24 h after the incubation has been initiated. Maximal binding is typically observed at 72–96 h (5, 8–10). (4) The induction and the maintenance of the LH/CG-R in GC requires the continual presence of FSH. If FSH is removed at any time, the levels of LH/CG-R return to basal within 24 h (4). Thus, the induction process does not involve a “committed step,” but is a continuous process. (5) The FSH-dependent increase in cell-surface LH/CG-R in GC is not due to the mobilization of an intracellular pool of preformed receptors to the cell surface (11). (6) The FSH-dependent increase in LH/CG-R can be prevented when protein synthesis is inhibited (11).

Keywords

Luteinizing Hormone Granulosa Cell mRNA Content Luteinizing Hormone Receptor Leydig Tumor 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.

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References

  1. 1.
    Richards JS, Ireland JJ, Rao MC, Bernath GA, Midgley AR, Jr. Ovarian follicular development in the rat: hormone receptor regulation by estradiol, follicle stimulating hormone and luteinizing hormone. Endocrinology 1976; 99: 1562–70.PubMedCrossRefGoogle Scholar
  2. 2.
    Uilenbroek JTJ, Richards JS. Ovarian follicular development during the rat estrous cycle: gonadotropin receptors and follicular responsiveness. Biol Reprod 1979; 20: 1159–65.PubMedCrossRefGoogle Scholar
  3. 3.
    Richards JS, Kersey KA. Changes in theca and granulosa cell function in antral follicles developing during pregnancy in the rat: gonadotropin receptors, cyclic AMP, and estradiol-17(3. Biol Reprod 1989; 21: 1185–1201.CrossRefGoogle Scholar
  4. 4.
    Segaloff DL, Limbird LE. Luteinizing hormone receptor appearance in cultured porcine granulosa cells requires continual presence of follicle-stimulating hormone. Proc Natl Acad Sci USA 1983; 80: 5631–5.PubMedCrossRefGoogle Scholar
  5. 5.
    Knecht M, Catt KJ. Induction of luteinizing hormone receptors by adensoine 3’,5’monophosphate in cultured granulosa cells. Endocrinology 1982; 111: 1192–1200.PubMedCrossRefGoogle Scholar
  6. 6.
    Nimrod A. The induction of ovarian LH-receptors by FSH is mediated by cyclic AMP. FEBS Lett 1981; 131: 31–3.PubMedCrossRefGoogle Scholar
  7. 7.
    Erickson GF, Wang C, Casper R, Mattson G, Hofeditz C. Studies on the mechanism of LH receptor control by FSH. Mol Cell Endocrinol 1982; 27: 17–30.PubMedCrossRefGoogle Scholar
  8. 8.
    Segaloff DL, May J, Schomberg DW, Limbird L. A model system for the biochemical study of luteinizing hormone/chorionic gonadotropin receptor synthesis. Acta Biochim Biophys Hung 1984; 804: 31–6.CrossRefGoogle Scholar
  9. 9.
    Sanders MM, Midgley AR, Jr. Rat granulosa cells differentiation: an in vitro model. Endocrinology 1982; 111: 614–24.PubMedCrossRefGoogle Scholar
  10. 10.
    Erickson GF, Wang C, Hsueh AJW. FSH induction of functional LH receptors in granulosa cells cultured in a chemically defined medium. Nature 1979; 279: 336–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Segaloff DL, Limbird LE. The cAMP-dependent induction of LH receptors in primary cultures of porcine granulosa cells is not due to the expression of an intracellular pool of LH receptors. Endocrinology 1983; 113: 825–7.PubMedCrossRefGoogle Scholar
  12. 12.
    McFarland KC, Sprengel R, Phillips HS, et al. Lutropin-choriogonadotropin receptor: an unusual member of the G protein-coupled receptor family. Science 1989; 245: 494–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Segaloff DL, Sprengel R, Nikolics K, Ascoli M. The structure of the lutropin/ choriogonadotropin receptor. Recent Prog Horm Res 1990; 46: 261–303.PubMedGoogle Scholar
  14. 14.
    Loosfelt H, Misrahi M, Atger M, et al. Cloning and sequencing of porcine LHhCG receptor cDNA: variants lacking transmembrane domain. Science 1989; 245: 525–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Segaloff DL, Wang H, Richards JS. Hormonal regulation of LH/CG receptor mRNA in rat ovarian cells during follicular development and luteinization. Mol Endocrinol (in press).Google Scholar
  16. 16.
    Channing CP, Dammerman S. Characteristics of gonadotropin receptors of porcine granulosa cells during follicle maturation. Endocrinology 1973; 114: 1114–23.Google Scholar
  17. 17.
    Jonassen JA, Richards JS. Granulosa cell desensitization: effects of gonadotropins on antral and preantral follicles. Endocrinology 1981; 106: 1786–94.CrossRefGoogle Scholar
  18. 18.
    Rao MC, Richards JS, Midgely AR, Jr, Reichen LE, Jr. Regulation of gonadotropin receptors by luteinizing hormone in granulosa cells. Endocrinology 1977; 101: 512–23.PubMedCrossRefGoogle Scholar
  19. 19.
    Schwall RH, Erickson GF. A new in vitro model system for the study of luteinizing hormone receptor down-regulation. J Biol Chem 1983; 258: 3442–5.PubMedGoogle Scholar
  20. 20.
    Ascoli M. Functions and regulation of cell surface receptors in cultured Leydig tumor cells. In: Conn PM, ed. The receptors. Boca Raton, FL: Academic Press, 1985: 368–400.Google Scholar
  21. 21.
    Ascoli M. Characterization of several clonal lines of cultured Leydig tumor cells: gonadotropin receptors and steroidogenic responses. Endocrinology 1981; 108: 88–95.PubMedCrossRefGoogle Scholar
  22. 22.
    Wang H, Segaloff DL, Ascoli M. Two distinct pathways for the lutropin/ choriogonadotropin (LH/CG)-induced down-regulation of the LH/CG receptor: receptor-mediated endocytosis and a cAMP-dependent reduction in receptor mRNA. J Biol Chem (in press).Google Scholar
  23. 23.
    Lloyd CE, Ascoli M. On the mechanisms involved in the regulation of the cell surface receptors for human choriogonadotropin and mouse epidermal growth factor in cultured Leydig tumor cells. J Cell Biol 1983; 96: 521–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Freeman DA, Ascoli M. Desensitization to gonadotropins in cultured Leydig tumor cells involves loss of gonadotropin receptors and decreased capacity for steroidogenesis. Proc Natl Acad Sci USA 1981; 78: 6309–13.PubMedCrossRefGoogle Scholar
  25. 25.
    Rebois RV, Fishman PH. Down-regulation of gonadotropin receptors in a murine Leydig tumor cell line. J Biol Chem 1984; 259: 3096–101.PubMedGoogle Scholar
  26. 26.
    Wang H, Ascoli M. Reduced gonadotropin responses in a novel clonal strain of Leydig tumor cells established by transfection of MA-10 cells with a mutant gene of the type I regulatory subunit of the cAMP-dependent protein kinase. Mol Cell Endocrinol 1990; 4: 80–90.CrossRefGoogle Scholar
  27. 27.
    Ascoli M. Internalization and degradation of receptor-bound human choriogonadotropin in Leydig tumor cells. Fate of the hormone subunits. J Biol Chem 1982; 257: 13306–11.PubMedGoogle Scholar
  28. 28.
    Ascoli M. Lysosomal accumulation of the hormone-receptor complex during receptor-mediated endocytosis of human choriogonadotropin. J Cell Biol 1984; 99: 1242–50.PubMedCrossRefGoogle Scholar
  29. 29.
    Ascoli M, Segaloff DL. On the fates of receptor-bound human ovine luteinizing hormone and human choriogonadotropin in cultured Leydig tumor cells. Demonstration of similar rates of internalization. Endocrinology 1987; 120: 1161–72.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 1992

Authors and Affiliations

  • Deborah L. Segaloff
  • JoAnne S. Richards
  • Mario Ascoli
  • Haiyun Wang

There are no affiliations available

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