Insulin-Like Growth Factors (IGFs) as Autocrine/Paracrine Regulators in the Porcine Ovarian Follicle

  • J. M. Hammond
  • J. S. Mondschein
  • S. F. Canning


Our laboratory was attracted to ovarian growth factors as a potential mechanism for regulating the growth and development of the ovarian follicle. At the time we began our studies, it was known that peptide growth factors were potent mitogens for granulosa cells of the pig and other species (1,2). In addition, insulin at high concentrations was known to influence granulosa cell growth and differentiation (3), but effects of IGFs on ovarian cells had not been shown. In the process of investigating the hormonal regulation of the growth-related enzyme ornithine decarboxylase, we discovered that the IGF multiplication stimulating activity (MSA, rat IGF-II) was an extremely potent stimulator of this activity in porcine granulosa cells and was considerably more potent than insulin (4,5). As reviewed below, the characterization of IGF effects on granulosa cell replication and the interaction of the insulin-like factors with other growth factors on these responses has continued to be an interest of our laboratory. In addition, studies from our group (6), as well as more numerous data from others represented at this symposium, indicated that the IGFs had stimulatory effects on the cytodifferentiation of ovarian cells. Accordingly recent studies have focused on the relative importance of the growth-promoting and steroidogenic effects of insulin-like factors on porcine granulosa cells.


Granulosa Cell Progesterone Secretion Porcine Granulosa Cell Porcine Ovary Multiplication Stimulate Activity 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Gospodarowicz D, Ill CR, Birdwell CR. Effects of fibroblast and epidermal growth factors on ovarian cell proliferation in vitro. I. Characterization of the response of granulosa cells to FGF and EGF. Endocrinology 1977; 100:1108–20.PubMedCrossRefGoogle Scholar
  2. 2.
    Gospodarowicz D, Bialecki H. Fibroblast and epidermal growth factors are mitogenic agents for cultured granulosa cells of rodent, porcine, and human origin. Endocrinology 1979; 104:757–64.PubMedCrossRefGoogle Scholar
  3. 3.
    Charming CP, Tsai V, Sachs D. Role of insulin, thyroxine and Cortisol in luteinization of porcine granulosa cells grown in chemically defined media. Biol Reprod 1976; 15:235–47.CrossRefGoogle Scholar
  4. 4.
    Veldhuis JD, Hammond JM. Multiplication stimulating activity regulates ornithine decarboxylase in isolated porcine granulosa cells in vitro. Endocr Res Commun 1979; 6:299–309.PubMedCrossRefGoogle Scholar
  5. 5.
    Hammond JM, Yoshida K, Veldhuis JD, Rechler MM, Knight AB. Intrafollicular role of somatomedins: comparison with effects of insulin. In: Greenwald GS, Terranova P, eds. Factors regulating ovarian function. New York: Raven Press, 1983:197–201.Google Scholar
  6. 6.
    Baranao JLS, Hammond JM. Comparative effects of insulin and insulin-like growth factors on DNA synthesis and differentiation of porcine granulosa cells. Biochem Biophys Res Commun 1984; 124:484–90.PubMedCrossRefGoogle Scholar
  7. 7.
    Tissue growth factors. Daughaday WH, ed. Clinics in endocrinology and metabolism; vol 13, no 1. Philadelphia: WB Saunders Company, 1984.Google Scholar
  8. 8.
    Hammond JM, Veldhuis JD, Seale TW, Rechter MM. Intraovarian regulation of granulosa-cell replication. In: Charming CP, Segal, eds. Intraovarian control mechanisms. New York: Plenum Publishing Company, 1982:341–56.CrossRefGoogle Scholar
  9. 9.
    Hammond JM, Baranao JLS, Skaleris D, Knight AB, Romanus JA, Rechter MM. Production of insulin-like growth factors by ovarian granulosa cells. Endocrinology 1985;117:2553–5.PubMedCrossRefGoogle Scholar
  10. 10.
    Hammond JM, Hsu C-J, Klindt J, Tsang BK, Downey BR. Gonadotropins increase concentrations of immunoreactive insulin-like growth factor-I in porcine follicular fluid in vivo. Biol Reprod 1988; 38:304–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Hsu C-J, Hammond JM. Gonadotropins and estradiol stimulate immunoreactive insulin-like growth factor-I production by porcine granulosa cells in vitro. Endocrinology 1987; 120:198–207.PubMedCrossRefGoogle Scholar
  12. 12.
    Hsu C-J, Hammond JM. Concomitant effects of growth hormone on secretion of insulin-like growth factor-I and progesterone by cultured porcine granulosa cells. Endocrinology 1987; 121:1343–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Mondschein JS, Hammond JM. Growth factors regulate immunoreactive insulin-like growth factor-I production by cultured porcine granulosa cells. Endocrinology 1988, 123:463–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Mondschein JS, Canning SF, Hammond JM. Effects of transforming growth factor beta on the production of immunoreactive insulin-like growth factor-I and progesterone and on 3H-thymidine incorporation in porcine granulosa cell cultures. Endocrinology 1988 (in press).Google Scholar
  15. 15.
    Davoren JB, Hsueh AJW. Growth hormone increases ovarian levels of immunoreactive somatomedin C/insulin-like growth factor I in vivo. Endocrinology 1986; 118:888–90.PubMedCrossRefGoogle Scholar
  16. 16.
    Hernandez ER, Hoyt E, Van Wyk JJ, Adashi EY. The somatomedin-C/insulin-like growth factor-I (Sm-C/IGF-I) gene is expressed in the rat ovary. Annual Meeting of the Endocrine Society, 1987.Google Scholar
  17. 17.
    Voutilainen R, Miller WL. Coordinate tropic hormone regulation of mRNAs for insulin-like growth factor II and the cholesterol side-chain-cleavage enzyme, P450scc, in human steroidogenic tissues. Proc Natl Acad Sci USA 1987; 84:1590–4.PubMedCrossRefGoogle Scholar
  18. 18.
    Ramasharma K, Cabrera CM, Li CH. Identification of insulin-like growth factor-II in human seminal and follicular fluids. Biochem Biophys Res Commun 1986; 140:536–42.PubMedCrossRefGoogle Scholar
  19. 19.
    Ramasharma K, Li CH. Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells. Proc Natl Acad Sci USA 1987; 84:2643–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Baranao JLS, Hammond JM. Serum-free medium enhances growth and differentiation of cultured pig granulosa cells. Endocrinology 1985; 116:51–8.CrossRefGoogle Scholar
  21. 21.
    Hammond JM, English HF. Regulation of deoxyribonucleic acid synthesis in cultured porcine granulosa cells by growth factors and hormones. Endocrinology 1987; 120:1309–46.CrossRefGoogle Scholar
  22. 22.
    Hammond JM, Hsu C-J, Mondschein JS, Canning SF. Paracrine and autocrine functions of growth factors in the ovarian follicle. J Anim Sci 1988; 66:21–31.Google Scholar
  23. 23.
    Murphy LJ, Bell GI, Friesen HG. Tissue distribution of insulin-like growth factor I and II messenger ribonucleic acid in the adult rat. Endocrinology 1987; 120:1279–82.PubMedCrossRefGoogle Scholar
  24. 24.
    Mondschein JS, Canning SF, Hammond JM. Profiles of immunoreactive (i) insulin-like growth factors (IGFs) -I and -II in porcine follicular fluid (FF) and granulosa cell conditioned medium (GCCM) [Abstract]. Biol Reprod 1988; 38(suppl 1):191.Google Scholar
  25. 25.
    Han VKM, Hill DJ, Strain AJ, et al. Identification of somatomedin/insulin-like growth factor immunoreactive cells in the human fetus. Pediatr Res 1987; 22:245–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Morgan DO, Edman JC, Standring DN, et al. Insulin-like growth factor II receptor as a multifunctional binding protein. Nature 1987; 329:301–7.PubMedCrossRefGoogle Scholar
  27. 27.
    MacDonald RG, Pfeffer SR, Coussens L, et al. A single receptor binds both insulin-like growth factor II and mannose-6-phosphate. Science 1988; 239:1134–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Bryan KA, Hammond JM, Canning S, et al. Reproductive and growth responses of gilts to exogenous porcine pituitary growth hormone. J Anim Sci 1988 (in press).Google Scholar
  29. 29.
    Baranao JLS, Hammond JM. Multihormone regulation of steroidogenesis in cultured porcine granulosa cells: studies in serum-free medium. Endocrinology 1985; 116:2143–51.PubMedCrossRefGoogle Scholar
  30. 30.
    Ledwitz-Rigby F, Petito SH, Tyner JK, Rigby BW. Follicular fluid effects on progesterone secretion are not due to follicle-stimulating hormone or steroids. Biol Reprod 1985; 33:277–85.PubMedCrossRefGoogle Scholar
  31. 31.
    Zumstein PP, Humbel RE. Purification of human insulin-like growth factors I and II. Methods Enzymol 1985; 109:782–8.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • J. M. Hammond
    • 1
  • J. S. Mondschein
    • 1
  • S. F. Canning
    • 1
  1. 1.Department of Medicine, The Milton S. Hershey Medical CenterThe Pennsylvania State UniversityHersheyUSA

Personalised recommendations