Gonadotrophin Control of Testicular Germ Cell Development

  • Gerhard F. Weinbauer
  • Eberhard Nieschlag
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 377)


The mammalian testis fulfills two main functions, i.e. the synthesis and release of the androgenic hormones (in particular testosterone) and the production of male gametes. In essence, testicular germ cell development is regulated by two mechanisms: by the action of endocrine factors from the pituitary and by the action of factors produced locally within the gonad (paracrine and autocrine factors).


Androgen Receptor Sertoli Cell Leydig Cell Seminiferous Tubule GnRH Antagonist 
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. Arslan M, Weinbauer GF, Schlatt S, Shahab M, Nieschlag E. Follicle-stimulating hormone and testosterone, alone or in combination, activate spermatogonial proliferation and stimulate testicular growth in the immature nonhuman primate (Macaca mulatto). J Endocrinol 1993; 136: 235–243.PubMedCrossRefGoogle Scholar
  2. Awoniyi CA, Santulli R, Chandrashekar V, Schanbacher BD, Zirkin BR. Quantitative restoration of advanced spermatogenic cells in adult male rats made azoospermic by active immunization against luteinizing hormone or gonadotropin-releasing hormone. Endocrinology 1989; 125: 1303–1309.PubMedCrossRefGoogle Scholar
  3. Awoniyi CA, Zirkin BR, Chandrashekar V. Exogenously administered testosterone maintains spermatogenesis in adult rats actively immunized against GnRH. Endocrinology 1992; 130: 3283–3288.PubMedCrossRefGoogle Scholar
  4. Behre HM, Böckers A, Schlingheider A, Nieschlag E. Sustained suppression of serum LH, FSH, and testosterone and increase of high-density lipoprotein cholesterol by daily injections of the GnRH antagonist cetrorelix over 8 days in normal men. Clin Endocrinol 1994; 40: 241–248.CrossRefGoogle Scholar
  5. Behre HM, Nieschlag E. Testosterone buciclate (20-Aet-l) in hypogonadal men: Pharmacokinetics and pharmacodynamics of the new long-acting testosterone ester. J Clin Endocrinol Metab 1992; 75: 1204–1210.PubMedCrossRefGoogle Scholar
  6. Behre HM, Oberpenning F, Nieschlag E. Comparative pharmacokinetics of androgen preparations: Application of computer analysis and simulation. In: Nieschlag E, Behre HM, eds. Testosterone — action, deficiency, substitution. Springer Verlag, Berlin, 1990:115–135.CrossRefGoogle Scholar
  7. Blok LJ, Bartlett JMS, Bolt-de-Vries J, Themmen APN, Brinkmann AO, Weinbauer GF, Nieschlag E, Grootegoed JA. Effect of testosterone deprivation on expression of the androgen receptor in rat prostate, epididymis and testis. Int J Androl 1992a; 15:182–198.PubMedCrossRefGoogle Scholar
  8. Blok LJ, Hoogerbrugge JW, Themmen APN, Baarends WM, Post M, Grootegoed JA. Transient down-regulation of androgen receptor messenger ribonucleic acid (mRNA) expression in Sertoli cells by follicle-stimulating hormone is followed by up-regulation of androgen receptor mRNA and protein. Endocrinology 1992b; 131:1243–1349.CrossRefGoogle Scholar
  9. Bremner WJ, Millar MR, Sharpe RM, Saunders PTK. Immunohistochemical localization of androgen receptors in the rat testis: Evidence for stage-dependent expression and regulation by androgens. Endocrinology 1994; 135: 1227–1234.PubMedCrossRefGoogle Scholar
  10. Cameron DF, Muffly KE. Hormonal regulation of spermatid binding. J Cell Sci 1991; 100: 623–633.PubMedGoogle Scholar
  11. Catt KF, Dufau ML. Gonadotropic hormones: biosynthesis, secretion, receptors and actions. In: Yen SSC, Jaffe RB, eds., Reproductive endocrinology. Physiology, pathophysiology and clinical management. Saunders Company, Philadelphia, 1991: 105–155).Google Scholar
  12. Chandolia RK, Weinbauer GF, Fingscheidt U, Bartlett JMS, Nieschlag E. Effects of flutamide on testicular involution induced by an antagonist of gonadotrophin-releasing hormone and on stimulation of spermatogenesis by follicle-stimulating hormone in rats. J Reprod Fertil 1991; 93: 313–323.PubMedCrossRefGoogle Scholar
  13. Grino PB, Griffin JE, Wilson JD. Testosterone at high concentrations interacts with the human androgen receptor similarly to dihydrotestosterone. Endocrinology 1990; 126: 1165–1172.PubMedCrossRefGoogle Scholar
  14. Gromoll J, Dankbar B, Sharma R, Nieschlag E. Molecular cloning of the testicular FSH receptor of the non-human primate Macaca fascicularis and identification of multiple transcripts in the testis. Biophys Biochem Res Comm 1993; 196: 1066–1072.CrossRefGoogle Scholar
  15. Gromoll J, Gudermann Th, Nieschlag E. Molecular cloning of a truncated isoform of the human follicle-stimulating hormone receptor. Biochem. Biophys Res Comm 1992; 188: 1077–1083.PubMedCrossRefGoogle Scholar
  16. Harsch IA, Simoni M, Nieschlag E. Molecular heterogeneity of serum follicle-stimulating hormone in hypogonadal patients before and during androgen replacement therapy and in normal men. Clin Endocrinol 1993; 39: 173–180.CrossRefGoogle Scholar
  17. Heckert L, Daley IJ, Griswold MD. Structural organization of the follicle-stimulating hormone receptor gene. Mol Endocrinol 1992; 6: 70–80.PubMedCrossRefGoogle Scholar
  18. Heckert LL, Griswold MD. Expression of follicle-stimulating hormone receptor mRNA in rat testes and Sertoli cells. Mol Endocrinol 1991; 5: 670–677.PubMedCrossRefGoogle Scholar
  19. Houde A, Lambert A, Saumande J, Silversides DW, Lussier JG. Structure of the bovine follicle-stimulating hormone receptor complementary DNA and expression in bovine tissues. Mol Reprod Dev 1994; 39: 127–135.PubMedCrossRefGoogle Scholar
  20. Hsueh AJW, LaPolt PS. Molecular basis of gonadotropin-receptor regulation. Trends Endocrinol Metab 1992; 3: 164–170.PubMedCrossRefGoogle Scholar
  21. Kerr JB, Maddocks S, Sharpe RM. Testosterone and FSH have independent, synergistic and stage-dependent effects upon spermatogenesis in the rat testis. Cell Tiss Res 1992; 269: 179–189.Google Scholar
  22. Kliesch S, Behre HM, Nieschlag E. High efficacy of gonadotropin or pulsatile gonadotropin-releasing hormone treatment in hypogonadotropic hypogonadal men. Eur J Endocrinol 1994, 131:347–354.PubMedCrossRefGoogle Scholar
  23. Kliesch S, Penttilä TL, Gromoll J, Saunders PTK; Nieschlag E. FSH receptor mRNA is expressed stage-dependently during spermatogenesis. Mol Cell Endocrinol 1992; 84:R45–R49.PubMedCrossRefGoogle Scholar
  24. Kremer H, Mariman E, Otten BJ, Moll GW jr, Stoelinga GBA, Wit JM, Jansen M, Drop SL, Faas B, Ropers H-H, Brunner HG. Cosegregation of missense mutations of the luteinizing hormone receptor gene with familial male-limited precocious puberty. Human Mol Gen 1993; 2: 1779–1783.CrossRefGoogle Scholar
  25. Lerchl A, Sotiriadou S, Behre HM, Pierce J, Weinbauer GF, Kliesch S, Nieschlag E. Restoration of spermatogenesis by follicle-stimulating hormone despite low intratesticular testosterone in photoinhibited hypogonadotropic Djungarian hamsters (Phodopus sungorus). Biol Reprod 1993; 49: 1108–1116.PubMedCrossRefGoogle Scholar
  26. Liri T, Herzmark P, Nakamoto JM, Van Dop C, Bourne HR. Rapid GDP release from Gsa in patients with gain and loss of endocrine function. Nature 1994; 371: 164–167.CrossRefGoogle Scholar
  27. Marshall GR, Wickings EJ, Nieschlag E. Testosterone can initiate spermatogenesis in an immature nonhuman primate, Macaca fascicularis. Endocrinology 1984; 114: 2228–2233.PubMedCrossRefGoogle Scholar
  28. Matsumoto AM, Bremner WJ. Control of spermatogenesis in humans. In: Moudgal NR, Yoshinaga K, Rao AY, Adiga PR, eds. Perspectives in Primate Reproductive Biology. Wiley Eastern Limited, New Delhi, 1990: 173–180).Google Scholar
  29. Meistrich ML. van Beek MEAB. Spermatogonial stem cells. In: Desjardins C, Ewing LL, eds. Oxford University Press, New York, 1993:266–295.Google Scholar
  30. Misrahi M, Thu Vu Hai M, Ghinea N, Loosfelt H, Meduri G, Atger M, Jolivet A, Gross B, Savouret J-F, Dessen Ph, Milgrom E. Molecular and cellular biology of gonadotropin receptors. In: Adashi EY, Leung PCK. eds. The Ovary. Raven Press New York, 1993:57–92.Google Scholar
  31. Moudgal NR, Ravindranath N, Murthy GS, Dighe RR, Aravindan GR, Martin F. Long-term contraceptive efficacy of vaccine of ovine follicle-stimulating hormone in male bonnet monkey (Macaca radiata). J Reprod Fertil 1992; 96: 91–102.PubMedCrossRefGoogle Scholar
  32. Muffly KE, Nazian SJ, Cameron DF. Effects of follicle-stimulating hormone on the junction-related Sertoli cell cytoskeleton and daily sperm production in testosterone-treated hypophysectomized rats. Biol Reprod 1994; 51: 158–166.PubMedCrossRefGoogle Scholar
  33. Nieschlag E, Behre HM, Simoni M, Gromoll J, Gudermann T. Endocrine regulation of testicular function in infertile men. In: Zirkin B, Whitcomb R, eds. International Symposium on Understanding Male Infertility: Basic and Clinical Approaches. Raven Press, New York, 1993: 113–119).Google Scholar
  34. Nieschlag E, Weinbauer GF, Behre HM. Hormonal male contraception: A real chance?. In: Nieschlag E, Habenicht UF (eds) Spermatogenesis — Fertilization — Contraception. Springer Verlag, Berlin, 1992; 169–200.CrossRefGoogle Scholar
  35. Nieschlag E. Care for the infertile male. Clin Endocrinol 1993; 38: 123–133.CrossRefGoogle Scholar
  36. Nieschlag E. Clinical relevance and irrelevance of molecular and cellular research on the testis. In: Verhoeven G, Habenicht UF (eds) Molecular and Cellular Endocrinology of the Testis. Springer Verlag, Berlin, 1994; 273–292.Google Scholar
  37. Niklowitz P, Khan S, Bergmann M, Hoffmann K, Nieschlag E. Differential effects of follicle-stimulating hormone and luteinizing hormone on Leydig cell function and restoration of spermatogenesis in hypophysectomized and photoinhibited Djungarian hamsters (Phodopus sungorus). Biol Reprod 1989; 41: 871–889.PubMedCrossRefGoogle Scholar
  38. Pickering BT, Ayad VJ, Birkett SD, CL Gilbert, Guldenaar SEF, Nicholson HD, Worley RTS, Wathes DC. Neurophyseal peptides in the gonads: are they real and do they have a function?Reprod Fertil Dev 1990; 2: 245–262.PubMedCrossRefGoogle Scholar
  39. Rommerts FFG. How much androgen is required for maintenance of spermatogenesis? J Endocrinol 1988; 116:1–6.CrossRefGoogle Scholar
  40. Ruizeveld de Winter JA, Trapman J, Vermey M, Mulder E, Zegers ND, van der Kwast TH. Androgen receptor expression in human tissues: an immunohistochemical study. J Histochem Cytochem 1991; 39: 927–936.CrossRefGoogle Scholar
  41. Russell LD, Griswold MD, eds. The Sertoli cell. Cache River Press, Clearwater, 1993.Google Scholar
  42. Schlatt S, Weinbauer GF, Arslan M, Nieschlag E. Appearance of α-smooth muscle actin in peritubular cells of monkey testes is induced by androgens, modulated by follicle stimulating hormone and maintained after hormonal withdrawal. J Androl 1993; 14: 340–350.PubMedGoogle Scholar
  43. Schlatt S, Weinbauer GF. Immunohistochemical localization of proliferating cell nuclear antigen as a tool to study cell proliferation in rodent and primate testis. Int J Androl 1994; 17: 214–222.PubMedCrossRefGoogle Scholar
  44. Sharpe RM. Regulation of spermatogenesis. In: Knobil E, Neill JD, eds. The Physiology of Reproduction. Raven Press, New York, 1994: 1363–1434).Google Scholar
  45. Sharpe RM. Testosterone and spermatogenesis. J Endocrinol 1987; 113: 1–2.PubMedCrossRefGoogle Scholar
  46. Shenker A, Laue L, Kosugi S, Merendino JJ jr, Minegishi T, Cutler GB jr. A constitutively activating mutation of the luteinizing hormone receptor in familial precocious puberty. Nature 1993; 365: 652–654.PubMedCrossRefGoogle Scholar
  47. Simoni M, Jockenhövel F, Nieschlag E. Polymorphisms of human pituitary FSH: Analysis of immunoreactivity and in-vitro bioactivity of different molecular species. J Endocrinol 1994, 141:359–367.PubMedCrossRefGoogle Scholar
  48. Srinath BR, Wickings EJ, Witting C, Nieschlag E. Active immunization with follicle-stimulating hormone for fertility control: A 4.5 year study in male rhesus monkeys. Fertil Steril 1983; 40: 110–117.PubMedGoogle Scholar
  49. Vliegen MK, Schlatt S, Weinbauer GF, Bergmann M, Groome NP, Nieschlag E. Localization of inhibin/activin subunits in the testis of adult nonhuman primates and men. Cell Tiss Res 1993; 273: 261–268.CrossRefGoogle Scholar
  50. Weinbauer GF, Behre HM, Fingscheidt U, Nieschlag E. Human follicle-stimulating hormone exerts a stimulatory effect on spermatogenesis, testicular size, and serum inhibin levels in the gonadotropin-releasing hormone antagonist-treated nonhuman primate (Macaca fascicularis). Endocrinology 1991; 129: 1831–1839.PubMedCrossRefGoogle Scholar
  51. Weinbauer GF, Göckeler E, Nieschlag E. Testosterone prevents complete suppression of spermatogenesis in the gonadotropin-releasing hormone (GnRH) antagonist-treated non-human primate (Macaca fascicularis). J Clin Endocrinol Metab 1988; 67: 284–290.PubMedCrossRefGoogle Scholar
  52. Weinbauer GF, Nieschlag E. Hormonal control of spermatogenesis. In: De Kretser DM, ed. Molecular Biology of the Male Reproductive System. Academic Press, New York, 1993: 99–143).Google Scholar
  53. Weinbauer GF, Nieschlag E. LH-RH antagonists: state of the art and future perspectives. In: Höffken K, ed. Peptides in Oncology. Springer Verlag, Berlin, 1992: 113–136).CrossRefGoogle Scholar
  54. Weinbauer GF, Nieschlag E. The role of testosterone in spermatogenesis. In: Nieschlag E, Behre HM, eds. Testosterone — action, deficiency, substitution. Springer Verlag, Berlin, 1990:23–51.CrossRefGoogle Scholar
  55. Whitcomb RW, Crowley WF. Clinical Review 4: Diagnosis and treatment of isolated gonadotropin-releasing hormone deficiency in men. J Clin Endocrinol Metab 1990; 70: 3–7.PubMedCrossRefGoogle Scholar
  56. WHO Task Force on Methods for the Regulation of Male Fertility. Comparison of two androgens plus depot-medroxyprogesterone acetate for suppression to azoospermia in Indonesian men. Fertil Steril 1993; 60: 1062–1068.Google Scholar
  57. WHO Task Force on Methods for the Regulation of Male Fertility. Contraceptive efficacy of testosterone-induced azoospermia in normal men. Lancet 1990; 336: 955–959.CrossRefGoogle Scholar
  58. Zirkin BR, Awoniyi C, Griswold MD, Russell LD, Sharpe RM. Is FSH required for adult spermatogenesis?J Androl 1994; 4: 273–276.Google Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Gerhard F. Weinbauer
    • 1
  • Eberhard Nieschlag
    • 1
  1. 1.Institute of Reproductive Medicine of the UniversityMünsterGermany

Personalised recommendations