Summary
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.
Similar content being viewed by others
References
Aherne WA, Dunnill MS (1982) Morphometry. Arnold, London
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 124:1217–1233
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 127:177–184
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 7:240–253
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 121:49–58
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 63:267–271
Corker CS, Davidson DW (1973) Radioimmunoassay of testosterone in various biological fluids without chromatography. J Steroid Biochem 9:373–374
Cunningham GR, Huckins C (1979) Persistence of complete spermatogenesis in the presence of low intrastesticular concentrations of testosterone. Endocrinology 105:177–186
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 27:47–57
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 8:43–51
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 44:363–375
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 43:325–342
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]:153
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 116:132–137
Kerr JB (1988) A light microscopic and morphometric analysis of the Sertoli cell during the spermatogenic cycle in the rat. Anat Embryol 177:341–348
Kerr JB, Donachie K, Rommerts FFG (1985) Selective destruction and regeneration of Leydig cells in vivo. Cell Tissue Res 242:145–156
Marshall GR, Wickings EJ, Ludecke DK, Nieschlag E (1984) Stimulation of spermatogenesis in stalk-sectioned Rhesus monkeys by testosterone alone. J Clin Endocrinol Metab 57:152–159
Marshall GR, Jockenhovel F, Ludecke D, Nieschlag E (1986) Maintenance of complete but quantitatively reduced spermatogenesis in hypophysectomized monkeys by testosterone alone. Acta Endocrinol 113:424–431
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 1:71–87
Matsumoto AM, Paulsen CA, Bremner WJ (1984) Stimulation of sperm production by human luteinizing hormone in gonadotrophin-suppressed men. J Clin Endocrinol Metab 59:882–887
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 62:1184–1192
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 425–432
Parvinen M, Vihko KK, Toppari J (1986) Cell interactions during the seminiferous epithelial cycle. Int Rev Cytology 104:115–151
Rommerts FFG (1988) How much androgen is required for maintenance of spermatogenesis? J Endocrinol 116:7–9
Russell LD, Clermont Y (1977) Degeneration of germ cells in normal, hypophysectomized and hormone treated hypophysectomized rats. Anat Rec 187:347–366
Russell LD, Malone JP, Karpas SL (1981) Morphological pattern elicited by agents affecting spermatogenesis by disruption of its hormonal stimulation. Tissue and Cell 13:369–380
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 126:95–102
Scowen EF (1938) The effect of androsterone and testosterone on the testes of hypophysectomized guinea pigs. Anat Rec [Suppl] 70:71–72
Sharpe RM (1987) Testosterone and spermatogenesis. J Endocrinol 113:1–2
Sharpe RM (1989) Follicle-stimulating hormone and spermatogenesis in the adult male. J Endocrinol 121:405–407
Sharpe RM, Bartlett JMS (1985) Stimulation of Leydig cell function by a polypeptide present in testicular interstitial fluid. Med Biol 63:245–250
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 117:19–26
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 11:507–523
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 188:3–20
Skinner MK, Fritz IB (1985a) Testicular peritubular cells secrete a protein under androgen control that modulates Sertoli cell functions. Proc Natl Acad Sci USA 82:114–118
Skinner MK, Fritz IB (1985b) Androgen stimulation of Sertoli cell function is enhanced by peritubular cells. Mol Cell Endocrinol 40:115–122
Steinberger E (1971) Hormonal control of mammalian spermatogenesis. Physiol Rev 51:1–22
Sun YT, Irby DC, Robertson DM, Kretser DM de (1989) The effects of exogenously administered testosterone on spermatogenesis in intact and hypophysectomized rats. Endocrinology 125:1000–1010
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 127:1215–1223
Verhoeven G, Cailleau J (1988) Follicle-stimulating hormone and androgens increase the concentration of the androgen receptor in Sertoli cells. Endocrinology 122:1541–1550
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 42:77–94
Woods MC, Simpson ME (1961) Pituitary control of the testis of the hypophysectomized rat. Endocrinology 69:91–125
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 124:3043–3049
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kerr, J.B., Maddocks, S. & Sharpe, R.M. Testosterone and FSH have independent, synergistic and stage-dependent effects upon spermatogenesis in the rat testis. Cell Tissue Res 268, 179–189 (1992). https://doi.org/10.1007/BF00338067
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00338067