Regulation of DNA Synthesis in Leydig Cells

  • Shafiq A. Khan
  • Katja Teerds
  • Jennifer Dorrington
Part of the Serono Symposia, USA book series (SERONOSYMP)


In the testis, the gonadotropins LH and FSH are required in vivo for the normal growth and differentiation of the Leydig cells and the Sertoli cells, respectively (1, 2). As a result of the actions of the gonadotropins on the somatic cells of the testis, the appropriate microenvironment is established in the seminiferous tubule that is conducive to the initiation and progression of spermatogenesis (3). LH acts on Leydig cells to stimulate the synthesis and secretion of testosterone, which then acts as a paracrine factor that is essential for spermatogenesis to proceed (4, 5). In intact rats that lack detectable levels of LH, administration of testosterone alone can maintain normal spermatogenesis (6, 7).


Sertoli Cell Leydig Cell Seminiferous Tubule Prepubertal Period Deoxyribonucleic Acid Synthesis 
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.
    Greep RO, Fevold HL, Hisaw FL. Effect of two hypophyseal gonadotropic hormones on the reproductive system of the male rat. Anat Rec 1936;65: 261–71.CrossRefGoogle Scholar
  2. 2.
    Christensen AK. Leydig cells. In: Hamilton DW, Greep RO, eds. Handbook of physiology; vol 5. Washington, DC: American Physiological Society, 1975:57–94.Google Scholar
  3. 3.
    Dorrington JH, Armstrong DT. Effects of FSH on gonadal functions. Recent Prog Horm Res 1979;35:301–42.PubMedGoogle Scholar
  4. 4.
    Ahmed N, Haltmeyer GC, Eik-Nes KB. Maintenance of spermatogenesis in rats with intratesticular implants containing testosterone or dihydrotestosterone (DHT). Biol Reprod 1973;8:411–9.Google Scholar
  5. 5.
    Sharpe RM. Testosterone and spermatogenesis. J Endocrinol 1987;113:1–3.PubMedCrossRefGoogle Scholar
  6. 6.
    Santulli R, Sprando RL, Awoniyi CA, Ewing EL, Zirkin BR. To what extent can spermatogenesis be maintained in the adult hypophysectomized rat testis with exogenously administered testosterone? Endocrinology 1990;126: 95–101.PubMedCrossRefGoogle Scholar
  7. 7.
    Awoniyi CA, Sprando RL, Santulli R, Chandrashekar V, Ewing LL, Zinlin BR. Restoration of spermatogenesis by exogenously administered testosterone in rats made azoospermic by hypophysectomy of withdrawal of luteinizing hormone alone. Endocrinology 1990;127:177–84.PubMedCrossRefGoogle Scholar
  8. 8.
    Mendis-Handagama SMLC, Risbridger GP, de Kretser DM. Morphometric analysis of the components of the neonatal and the adult rat testis interstitium. Int J Androl 1987;10:525–34.PubMedCrossRefGoogle Scholar
  9. 9.
    Hardy MP, Zirkin BR, Ewing LL. Kinetic studies on the development of the adult population of Leydig cells in testis of the pubertal rat. Endocrinology 1989;124:762–70.PubMedCrossRefGoogle Scholar
  10. 10.
    de Kretser DM, Kerr JB. The cytology of the testis. In: Knobil E, Neill J, eds. The physiology of reproduction. New York: Raven Press, 1988:837–932.Google Scholar
  11. 11.
    Kerr JB, Knell CM. The fate of fetal Leydig cells during the development of the fetal and postnatal rat testis. Development 1988;103:535–44.PubMedGoogle Scholar
  12. 12.
    Tapanaien J, Kuopio T, Pelliniemi LJ, Huhtaniemi I. Rat testicular endogenous steroids and number of Leydig cells between the fetal period and sexual maturity. Biol Reprod 1984;31:1027–35.CrossRefGoogle Scholar
  13. 13.
    Teerds KJ, Closset J, Rommerts FFG, et al. Effects of pure FSH and LH preparations on the number and function of Leydig cells in immature hypophysectomized rats. J Endocrinol 1989;120:97–106.PubMedCrossRefGoogle Scholar
  14. 14.
    Sharpe RM, Maddocks S, Kerr JB. Cell-cell interaction in the control of spermatogenesis as studied using Leydig cell destruction and testosterone replacement. Am J Anat 1990;188:3–20.PubMedCrossRefGoogle Scholar
  15. 15.
    Pledger WJ. Regulation of cell proliferation: serum growth factors control an ordered series of G1 events. In: Veneziale CM, ed. Control of cell growth and proliferation. New York: Van Nostrand-Reinhold, 1985:108–31.Google Scholar
  16. 16.
    Khan S, Teerds K, Dorrington J. Growth factor requirements for DNA synthesis by Leydig cells from the immature rat. Biol Reprod 1992;46:335–41.PubMedCrossRefGoogle Scholar
  17. 17.
    Handelsman DJ, Spaliviera JA, Scott CD, Baxter RC. Identification of insulin-like growth factor-I and its receptors in the rat testis. Acta Endocrinol 1985;109:543–9.PubMedGoogle Scholar
  18. 18.
    Verhoeven G, Gailleau J. Stimulatory effects of epidermal growth factor on steroidogenesis in Leydig cells. Mol Cell Endocrinol 1986;47:99–106.PubMedCrossRefGoogle Scholar
  19. 19.
    Khan SA, Schmidt K, Hallin P, DiPauli R, De Geyter Ch, Nieschlag E. Human testis cytosol and ovarian follicular fluid contain high amount of interleukin-1-like factor(s). Mol Cell Endocrinol 1988;58:221–30.PubMedCrossRefGoogle Scholar
  20. 20.
    Khan SA, Soder O, Syed V, Gustafsson K, Lindh M, Ritzen EM. The rat testis produces large amount of an interleukin-1-like factor. Int J Androl 1987;10:495–503.PubMedCrossRefGoogle Scholar
  21. 21.
    Calkins JH, Guo H, Sigel MM, Lin T. Tumor necrosis factor-alpha enhances inhibitory effects on interleukin-1 beta on Leydig cell steroidogenesis. Biochem Biophys Res Commun 1990;166:1313–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Pollänen P, Söder O, Parvinen M. Interleukin-lα stimulation of spermatogonial proliferation in vivo. Reprod Fertil Dev 1989;1:85–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Parvinen M, Söolev O, Mali P, Fröysa B, Ritzen EM. In vitro stimulation of stage-specific deoxyribonucleic acid synthesis in rat seminiferous tubule segments by interleukin-1α. Endocrinology 1991;129:1614–20.PubMedCrossRefGoogle Scholar
  24. 24.
    Takao T, Mitchell WM, Tracey DE, DeSouza EB. Identification of interleukin-1 receptors in the mouse testis. Endocrinology 1990;127:251–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Khan SA, Khan SJ, Dorrington JH. Interleukin-1 stimulates deoxyribonucleic acid synthesis in immature rat Leydig cell in vitro. Endocrinology 1992; 131: 1853–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Gerard N, Syed V, Bardin W, Genelet N, Jegou B. Sertoli cells are the site of interleukin-la synthesis in rat testis. Mol Cell Endocrinol 1991;82:R13–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Christensen AK, Gillim SW. The correlation of fine structure and function in steroid-secreting cells with emphasis on those of the gonads. In: Mckerns KW, ed. The gonads. New York: Appleton-Century-Crofts, 1969:415–88.Google Scholar
  28. 28.
    Yee JB, Hutson JC. Effects of testicular macrophage-conditioned medium on Leydig cells in culture. Endocrinology 1985;116:2682–4.PubMedCrossRefGoogle Scholar
  29. 29.
    Wang D, Nagpal M, Calkins JH, Chang W, Sigel MM, Lin T. Interleukin-lβ induces interleukin-1α messenger ribonucleic acid expression in primary cultures of Leydig cells. Endocrinology 1991;129:2862–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Khan SA, Hallin P, Bartlett J, DeGeyter Ch, Nieschlag E. Characterization of a factor from ovarian follicular fluid which stimulates Leydig cell testosterone production. Acta Endocrinol (Copenh) 1988;188:283.Google Scholar
  31. 31.
    Khan SA, Keck C, Gudermann T, Nieschlag E. Isolation of a protein from human ovarian follicular fluid which exerts major stimulatory effects on in vitro steroid production of testicular ovarian and adrenal cells. Endocrinology 1990;126:3034–52.Google Scholar
  32. 32.
    Khan SA, Keck C, Nieschlag E. Stimulation of Leydig cells steroidogenesis by a factor from human ovarian follicular fluid. In: Findlay J, Haseltine H, eds. Growth factors in fertility regulation. UK: Cambridge University Press, 1991:185–93.Google Scholar
  33. 33.
    Khan SA, Teerds KJ, Dorrington JH. Steroidogenesis-inducing protein promotes deoxyribonucleic acid synthesis in Leydig cells from immature rats. Endocrinology 1992;130:599–606.PubMedCrossRefGoogle Scholar
  34. 34.
    Watrin T, Scotto L, Assoian RK, Wolgemuth DJ. Cell lineage specificity of expression of the murine transforming growth factor-β3, and transforming growth factor-β1 genes. Cell Growth Differ 1991;2:77–83.PubMedGoogle Scholar
  35. 35.
    Mullaney BP, Glenn B, Skinner MK. Cell-cell interactions in the testis: the role of transforming growth factors [Abstract 520]. Biol Reprod 1991; 44(suppl 1).Google Scholar
  36. 36.
    Skinner MK, Moses HL. Transforming growth factor-β gene expression and action in the seminiferous tubule: peritubular cell-Sertoli cell interactions. Mol Endocrinol 1989;3:625–34.PubMedCrossRefGoogle Scholar
  37. 37.
    Benahmed M, Sondoillet C, Chauvin MA, DePeretti E, Morena AM. On the mechanisms involved in the inhibitory and stimulating actions of transforming growth factor-β on porcine testicular steroidogenesis: an in vitro study. Mol Cell Endocrinol 1989;67:155–64.PubMedCrossRefGoogle Scholar
  38. 38.
    Bendell JJ, Dorrington JH. Epidermal growth factor influences growth and differentiation of rat granulosa cells. Endocrinology 1990;127:533–40.PubMedCrossRefGoogle Scholar
  39. 39.
    Lobb DK, Dorrington JH. Intraovarian regulation of follicular development. Anim Reprod Sci 1992;28:343–54.CrossRefGoogle Scholar
  40. 40.
    Teerds KJ, Rommerts FFG, Dorrington JH. Immunohistochemical detection of transforming growth factor-α in Leydig cell during the development of the rat testis. Mol Cell Endocrinol 1990;69:R1–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Teerds KJ, Dorrington JH. Localization of transforming growth factor β1 and β2 during testicular development in the rat. Biol Reprod 1993;48:40–5.PubMedCrossRefGoogle Scholar
  42. 42.
    Khan SA, Dorrington JH, Moran MF. Steroidogenesis-inducing protein stimulates protein-tyrosine kinase activity in rat Leydig cells. Endocrinology 1993;132:109–14.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 1994

Authors and Affiliations

  • Shafiq A. Khan
  • Katja Teerds
  • Jennifer Dorrington

There are no affiliations available

Personalised recommendations