Cell and Tissue Research

, Volume 268, Issue 1, pp 179–189 | Cite as

Testosterone and FSH have independent, synergistic and stage-dependent effects upon spermatogenesis in the rat testis

  • J. B. Kerr
  • S. Maddocks
  • R. M. Sharpe


Adult rats were hypophysectomized and treated with ethane dimethanesulphonate (EDS) selectively to eliminate the Leydig cells in the testis. By removing the source of endogenous gonadotrophins and androgens, the subsequent effects on the seminiferous epithelium were studied after 20 days of treatment with vehicle, or FSH (2x50 μg/day) or a low dose of testosterone (0.6 mg testosterone esters every 3rd day) alone or in combination. Compared to vehicle-treated hypophysectomized rats with Leydig cells, testis weight in saline-treated hypophysectomized rats treated with EDS declined by 50%, spermatogenesis was disrupted severely and only 18% of the tubules contained spermatids, these being confined to stages I–VI of the spermatogenic cycle. Treatment with either FSH or testosterone esters alone significantly (P<0.01) increased testis weight compared to vehicle-treated hypophysectomized rats treated with EDS and 40% of tubules contained spermatids either at stages I–VI after FSH, or at all stages I–XIV after testosterone treatment. Treatment with FSH and testosterone esters together maintained testis weights approximately 20% above vehicle-treated hypophysectomized controls; over 70% of the seminiferous tubules contained spermatids and there was a marked stimulation of spermatogenesis at all stages of the spermatogenic cycle. The results suggest, that in the absence of the pituitary gland and the Leydig cells, FSH alone partially supports spermatogenesis up to the development of round spermatids whereas testosterone is capable of maintaining spermatid development at all 14 stages of the cycle. When FSH and testosterone were administered in combination, the effects upon spermatogenesis were far greater than the response expected if their individual effects were simply additive. It is therefore concluded that FSH may play a role in normal spermatogenesis and that this role is essentially that of augmenting the response of the testis to testosterone. The biochemical mechanisms via which this might occur are discussed and hypophysectomized rats treated with EDS used in the present studies should provide a useful approach for their identification.

Key words

Testis Spermatogenesis FSH Testosterone Rat (Sprague-Dawley) 


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  1. Aherne WA, Dunnill MS (1982) Morphometry. Arnold, LondonGoogle Scholar
  2. Awoniyi CA, Santulli R, Sprando RL, Ewing LL, Zirkin BR (1989) Restoration of advanced spermatogenic cells in the experimentally regressed rat testis: quantitative relationship to testosterone concentration within the testis. Endocrinology 124:1217–1233Google Scholar
  3. Awoniyi CA, Sprando RL, Santulli R, Chandrashekar V, Ewing LL, Zirkin BR (1990) Restoration of spermatogenesis by exogenously administered testosterone in rats made azoospermic by hypophysectomy or withdrawal of luteinizing hormone alone. Endocrinology 127:177–184Google Scholar
  4. Bartlett JMS, Kerr JB, Sharpe RM (1986) The effect of selective destruction and regeneration of rat Leydig cells on the intratesticular distribution of testosterone and morphology of the seminiferous epithelium. J Androl 7:240–253Google Scholar
  5. Bartlett JMS, Weinbauer GF, Nieschlag E (1989) Differential effects of FSH and testosterone on the maintenance of spermatogenesis in the adult hypophysectomized rat. J Endocrinol 121:49–58Google Scholar
  6. Blok LJ, Mackenbach P, Trapman J, Themmen APN, Brinkmann AO, Grootegoed JA (1989) Follicle-stimulating hormone regulates androgen receptor mRNA in Sertoli cells. Mol Cell Endocrinol 63:267–271Google Scholar
  7. Corker CS, Davidson DW (1973) Radioimmunoassay of testosterone in various biological fluids without chromatography. J Steroid Biochem 9:373–374Google Scholar
  8. Cunningham GR, Huckins C (1979) Persistence of complete spermatogenesis in the presence of low intrastesticular concentrations of testosterone. Endocrinology 105:177–186Google Scholar
  9. Elkington JSH, Blackshaw AW, (1974) Studies in testicular function. I. Quantitative effects of FSH, LH, testosterone and dihydrotestosterone on restoration and maintenance of spermatogenesis in the hypophysectomized rat. Aust J Biol Sci 27:47–57Google Scholar
  10. Gordeladze JO, Parvinen M, Clausen OP, Hansson V (1982) Stage dependent variation in Mn++sensitive adenylyl cyclase (AC) activity in spermatids and FSH-sensitive AC in Sertoli cells. Arch Androl 8:43–51Google Scholar
  11. Hansson V, Weddington SC, McLean WS, Smith AA, Nayfeh SN, French FS, Ritzen EM (1975) Regulation of seminiferous tubular function by FSH and androgen. J Reprod Fertil 44:363–375Google Scholar
  12. Hess RA (1990) Quantitative and qualitative characteristics of the stages and transitions in the cycle of the rat seminiferous epithelium: light microscopic observations of perfusion-fixed and plastic embedded testes. Biol Reprod 43:325–342Google Scholar
  13. Huang L, Pogach E, Nathan W, Giglio W, Seebode JJ (1991) Synergism of FSH and testosterone on spermiogenesis in hypophysectomized rats (abstract). J Androl [Suppl 16]:153Google Scholar
  14. Isomaa V, Parvinen M, Janne OA, Bardin CW (1985) Nuclear androgen receptors in different stages of the seminiferous epithelial cycle and the interstitial tissue of rat testis. Endocrinology 116:132–137Google Scholar
  15. Kerr JB (1988) A light microscopic and morphometric analysis of the Sertoli cell during the spermatogenic cycle in the rat. Anat Embryol 177:341–348Google Scholar
  16. Kerr JB, Donachie K, Rommerts FFG (1985) Selective destruction and regeneration of Leydig cells in vivo. Cell Tissue Res 242:145–156Google Scholar
  17. Marshall GR, Wickings EJ, Ludecke DK, Nieschlag E (1984) Stimulation of spermatogenesis in stalk-sectioned Rhesus monkeys by testosterone alone. J Clin Endocrinol Metab 57:152–159Google Scholar
  18. Marshall GR, Jockenhovel F, Ludecke D, Nieschlag E (1986) Maintenance of complete but quantitatively reduced spermatogenesis in hypophysectomized monkeys by testosterone alone. Acta Endocrinol 113:424–431Google Scholar
  19. Matsumoto AM, Bremmer WJ (1987) Endocrinology of the hypothalamic-pituitary-testicular axis with particular reference to the hormonal control of spermatogenesis. Bailliére's Clin Endocrinol Metab 1:71–87Google Scholar
  20. Matsumoto AM, Paulsen CA, Bremner WJ (1984) Stimulation of sperm production by human luteinizing hormone in gonadotrophin-suppressed men. J Clin Endocrinol Metab 59:882–887Google Scholar
  21. Matsumoto AM, Karpas AE, Bremner WJ (1986) Chronic human chorionic gonadotropin administration in normal men: evidence that follicle-stimulating hormone is necessary for the maintenance of quantitatively normal spermatogenesis in man. J Clin Endocrinol Metab 62:1184–1192Google Scholar
  22. Parvinen M, Marana R, Robertson DM, Hansson V, Ritzen EM (1980) Functional cycle of rat Sertoli cells: differential binding and action of follicle-stimulating hormone at various stages of the spermatogenic cycle. In: Steinberger A, Steinberger E (eds) Testicular development, structure and function. Raven Press, New York, pp 425–432Google Scholar
  23. Parvinen M, Vihko KK, Toppari J (1986) Cell interactions during the seminiferous epithelial cycle. Int Rev Cytology 104:115–151Google Scholar
  24. Rommerts FFG (1988) How much androgen is required for maintenance of spermatogenesis? J Endocrinol 116:7–9Google Scholar
  25. Russell LD, Clermont Y (1977) Degeneration of germ cells in normal, hypophysectomized and hormone treated hypophysectomized rats. Anat Rec 187:347–366Google Scholar
  26. Russell LD, Malone JP, Karpas SL (1981) Morphological pattern elicited by agents affecting spermatogenesis by disruption of its hormonal stimulation. Tissue and Cell 13:369–380Google Scholar
  27. Santulli R, Sprando RL, Awoniyi CA, Ewing LL, Zirkin BA (1990) To what extent can spermatogenesis be maintained in the hypophysectomized adult rat testis with exogenously administered testosterone? Endocrinology 126:95–102Google Scholar
  28. Scowen EF (1938) The effect of androsterone and testosterone on the testes of hypophysectomized guinea pigs. Anat Rec [Suppl] 70:71–72Google Scholar
  29. Sharpe RM (1987) Testosterone and spermatogenesis. J Endocrinol 113:1–2Google Scholar
  30. Sharpe RM (1989) Follicle-stimulating hormone and spermatogenesis in the adult male. J Endocrinol 121:405–407Google Scholar
  31. Sharpe RM, Bartlett JMS (1985) Stimulation of Leydig cell function by a polypeptide present in testicular interstitial fluid. Med Biol 63:245–250Google Scholar
  32. Sharpe RM, Donachie K, Cooper I (1988a) Re-evaluation of the intratesticular level of testosterone required for quantitative maintenance of spermatogenesis in the rat. J Endocrinol 117:19–26Google Scholar
  33. Sharpe RM, Fraser HM, Ratnasooriya WD (1988b) Assessment of the role of Leydig cell products other than testosterone in spermatogenesis and fertility in adult rats. Int J Androl 11:507–523Google Scholar
  34. Sharpe RM, Maddocks S, Kerr JB (1990) Cell-cell interactions in the control of spermatogenesis as studied using Leydig cell destruction and testosterone replacement. Am J Anat 188:3–20Google Scholar
  35. Skinner MK, Fritz IB (1985a) Testicular peritubular cells secrete a protein under androgen control that modulates Sertoli cell functions. Proc Natl Acad Sci USA 82:114–118Google Scholar
  36. Skinner MK, Fritz IB (1985b) Androgen stimulation of Sertoli cell function is enhanced by peritubular cells. Mol Cell Endocrinol 40:115–122Google Scholar
  37. Steinberger E (1971) Hormonal control of mammalian spermatogenesis. Physiol Rev 51:1–22Google Scholar
  38. Sun YT, Irby DC, Robertson DM, Kretser DM de (1989) The effects of exogenously administered testosterone on spermatogenesis in intact and hypophysectomized rats. Endocrinology 125:1000–1010Google Scholar
  39. Sun YT, Wreford NG, Robertson DM, Kretser DM de (1990) Quantitative cytological studies of spermatogenesis in intact and hypophysectomized rats: identification of androgen-dependent stages. Endocrinology 127:1215–1223Google Scholar
  40. Verhoeven G, Cailleau J (1988) Follicle-stimulating hormone and androgens increase the concentration of the androgen receptor in Sertoli cells. Endocrinology 122:1541–1550Google Scholar
  41. Vernon RG, Go VLW, Fritz IB (1975) Hormonal requirements of the different cycles of the seminiferous epithelium during reinitiation of spermatogenesis in long-term hypophysectomized rats. J Reporod Fertil 42:77–94Google Scholar
  42. Woods MC, Simpson ME (1961) Pituitary control of the testis of the hypophysectomized rat. Endocrinology 69:91–125Google Scholar
  43. Zirkin BR, Santulli R, Awoniyi CA, Ewing LL (1989) Maintenance of advanced spermatogenic cells in the adult rat testis: quantitative relationship to testosterone concentration within the testis. Endocrinology 124:3043–3049Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • J. B. Kerr
    • 1
  • S. Maddocks
    • 2
  • R. M. Sharpe
    • 3
  1. 1.Department of AnatomyMonash UniversityClayton, MelbourneAustralia
  2. 2.Department of Animal SciencesWaite Agricultural Research InstituteGlen OsmondAustralia
  3. 3.MRC Reproductive Biology UnitCentre for Reproductive BiologyEdinburghUK

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