Cell and Tissue Research

, Volume 278, Issue 3, pp 595–600 | Cite as

Localization of follicle-stimulating hormone (FSH) immunoreactivity and hormone receptor mRNA in testicular tissue of infertile men

  • Tobias M. Böckers
  • Eberhard Nieschlag
  • Michael R. Kreutz
  • Martin Bergmann


Testicular biopsies from 82 oligo-or azoospermic male patients were subjected to immunostaining using anti-human FSH antibodies. Histological evaluation showed normal spermatogenesis (nspg) in 7 (FSH: 2.7±0.7), mixed atrophy (ma) in 63 (FSH:5.3±0.5), and bilateral or unilateral Sertoli Cell Only syndrome (SCO) in 12 (FSH:21.7±3.5) patients. For the relationship between FSH values and testicular histology, see Bergmann et al. (1994). FSH immunoreactivity was found exclusively in Sertoli cells and in some interstitial cells. Seminiferous epithelium showing normal or impaired spermatogenesis displayed only weak immunoreactivity compared to intense immunoreaction, i.e. large and numerous vesicles in Sertoli cells of SCO tubules in biopsies showing mixed atrophy or SCO. In addition, h-FSH receptor mRNA was demonstrated by in situ hydridization using biotinylated cDNA antisense oligonucleotides. Hybridization signals were found within the seminiferous epithelium exclusively in Sertoli cell cytoplasm associated with normal spermatogenesis and in epithelia showing different signs of impairment, including SCO. It is concluded that: (1) Sertoli cells are the only cells within the seminiferous epithelium expressing FSH receptors; (2) the accumulation of FSH immunoreactivity in Sertoli cells of SCO tubules appears to be a sign of impaired Sertoli cell function.

Key words

FSH Immunohistochemistry Receptor mRNA In situ hybridization Sertoli cell Testis Human 


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  1. Almiron I, Domene H, Chemes HE (1984) The hormonal regulation of premeiotic steps of spermatogenesis in the newborn rat. J Androl 5:235–242Google Scholar
  2. Baker HWG, Bremmer WJ, Burger HG, de Kretser DM, Dulmanis A, Eddie LW, Hudson B, Keogh EJ, Lee VWK, Rennie GC (1976) Testicular control of follicle-stimulating hormone secretion. Rec Prog Horm Res 32:429–476Google Scholar
  3. Bergh A, Cajander S (1990) Immunohistochemical localization of inhibin alpha in the testes of normal men and in men with testicular disorders. Int J Androl 13:463–469Google Scholar
  4. Bergmann M, Behre HM, Nieschlag E (1994) Serum FSH and testicular morphology in male infertility. Clin Endocrinol 40:133–136Google Scholar
  5. Boitani C, Politi MG, Menna T (1993) Spermatogonial cell proliferation in organ culture of immature rat testis. Biol Reprod 48:761–767Google Scholar
  6. Bruning G, Dierichs R, Stümpel C, Bergmann M (1993) Sertolicell nuclear changes in human testicular biopsies as revealed by three dimensional reconstruction. Andrologia 25:311–316Google Scholar
  7. Chemes HE, Dym M, Raj HGM (1979) The role of gonadotrophins and testosterone on initiation of spermatogenesis in the immature rat. Biol Reprod 21:241–249Google Scholar
  8. Cordell JL, Falini B, Erber WN, Ghosh AK, Abdulaziz Z, Mac-Donald S, Pulford KAF, Stein H, Mason DY (1984) Immunoenzymatic labelling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP) complexes. J Histochem Cytochem 32:219–229Google Scholar
  9. De Kretser DM, Burger HG, Fortune D, Hudson B, Long AR, Paulsen CA, Taft HP (1972) Hormonal, histological and chromosomal studies in adult males with testicular disorders. J Clin Endocrinol Metab 35:392–401Google Scholar
  10. De Kretser DM, Burger HG, Hudson B (1974) The relationship between germinal cells and serum FSH levels in males with infertility. J Clin Endocrinol Metab 38:787–793Google Scholar
  11. De Kretser DM, Kerr JB, Paulsen CA (1981) Evaluation of the ultrastructural changes in the human Sertoli cell in testicular disorders and the relationship of the changes to the levels of serum FSH. Int J Androl 4:129–144Google Scholar
  12. Feig LA, Bellve AR, Erikson NH, Klagsbrun M (1980) Sertoli cells contain a mitogenic polypeptide. Proc Natl Acad Sci USA 77:4774Google Scholar
  13. Haneji T, Nishimune Y (1982) Hormones and the differentiation of type A spermatogonia in mouse cryptorchid testes incubated in vitro. J Endocr 94:43–50Google Scholar
  14. Holstein AF, Schirren C (1983) Histological evaluation of testicular biopsies. In: Schirren C, Holstein AF (eds) Fortschritte der Andrologie Vol 8. Grosse, Berlin, pp 108–117Google Scholar
  15. Honn CA, Gardner PJ, Leuschen MP (1983) Immunocytochemical staining of isolated rat Sertoli cells for anti-FSHβ. Am J Anat 167:441–450Google Scholar
  16. Hovatta O, Huhtaniemi I, Wahlström T (1986) Testicular gonadotrophins and their receptors in human crytorchidism as revealed by immunohistochemistry and receptor assay. Acta Endocrinol 111:128–132Google Scholar
  17. Huckins C, Mills N, Besch P, Means A (1973) Spermatogonial differentiation in immature rats. Regulation by FSH. Endocrinology 92:A-94Google Scholar
  18. Ishida H, Isuguri K, Aso Y, Takayasu H, Tamaoki B-I (1976) Endocrine studies in Sertoli-cell-only syndrome. J Urol 116: 56–58Google Scholar
  19. Jègou B (1993) The Sertoli-germ cell communication network in mammals. Int Rev Cytol. 147:25–96Google Scholar
  20. Jockenhövel F, Khan SA, Nieschlag E (1989) Diagnostic value of bioactive FSH in male infertility. Acta Endocrinol 121: 802–810Google Scholar
  21. Johnson L, Grumbles JS, Bagheri A, Petty CS (1990) Increased germ cell degereration during postprophase of meiosis is related to increased serum follicle-stimulating hormone concentrations and reduced daily sperm production in aged men. Biol Reprod 42:281–287Google Scholar
  22. Kancheva LS, Martinova YS, Georgiev VD (1990) Prepubertal Sertoli cells secrete a mitogenic factor(s) that stimulates germ and somatic cell proliferation. Mol Cell Endocrinol 69: 121–128Google Scholar
  23. Kliesch S, Penttilä T-L, Gromoll J, Saunders PTK, Nieschlag E, Parvinen M (1992) FSH receptor mRNA is expressed stagedependently during rat spermatogenesis. Mol Cell Endocrinol 84:R45-R49Google Scholar
  24. Kula L (1991) Hyperactivation of early steps in spermatogenesis comprises meiotic insufficiency in men with hypergonadotropism. A possible quantitative assay for high FSH/low testosterone availabilities. Andrologia 23:127–133Google Scholar
  25. Micic S, Ilic V, Genbacev O, Dotlic R (1983) Endocrine profile in 45 patients with Sertoli cell only syndrome. Andrologia 15:228–232Google Scholar
  26. Minegish T, Nakamura K, Takahura Y, Ibuki Y, Igarashi M (1991) Cloning and sequencing of human FSH receptor cDNA. Biochem Biophys Res Commun 3:1125–1130Google Scholar
  27. Niklowitz P, Khan S, Bergmann M, Hoffmann K, Nieschlag E (1989) 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 41: 871–880Google Scholar
  28. Okuyama A, Nonomura N, Koh E, Kondoh N, Nakamura M, Namiki M, Yoshida T, Fujioka H, Kiyohara H, Matsumoto K, Sonoda T (1989) Testicular FSH and hCG receptors in Sertolicell-only syndrome. Arch Androl 23:119–124Google Scholar
  29. Orth J, Christensen AK (1977) Localization of 125I-labeled FSH in the testes of hypophysectomized rats by autoradiography at the light and electron microscope levels. Endocrinology 101:262–267Google Scholar
  30. Orth J, Christensen AK (1978) Autoradiographic localization of specifically bound 125I-labeled follicle stimulating hormone on spermatogonia of the rat testis. Endocrinology 103: 1944–1951Google Scholar
  31. 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 spermatogenic cycle. In: Steinberger A, Steinberger E (eds) Testicular development structure and function. Raven Press, New York, pp 425–532Google Scholar
  32. Shimizu A, Kawashima S (1989) Kinetic study of internalization and degradation of 131 I-labelled follicle-stimulating hormone in mouse Sertoli cells and its relevance to other systems. J Biol Chem 264:13632–13638Google Scholar
  33. Shimizu A, Tsutsui K, Kawashima S (1987) Autoradiographic study of binding and internalization of follicle-stimulating hormone in the mouse testis minces in vitro. Endocrinol Japon 34:431–442Google Scholar
  34. Sinha Hikim AP, Sinha Hikim S, Amador AG, Bartke A, Woolf A, Russell LD (1991) Reinitiation of spermatogenesis by exogenous gonadotropins in a seasonal breeder, the woodchuck (Marmota monax), during gonadal inactivity. Am J Anat 192:194–213Google Scholar
  35. Tajima Y, Onoue H, Kitamura Y, Nishimune Y (1991) Biologically active kit ligand growth factor is produced by mouse Sertoli cells and is defective in Sld-mutant mice. Development 113:1031–1035Google Scholar
  36. Terada T, Hatekayama S (1991) Morphological evidence of two types of idiopathic Sertoli cell only syndrome. Int J Androl 14:108–116Google Scholar
  37. Van Alphen MMA, Van de Kant HJG, De Rooij DG (1988) Follicle-stimulating hormone stimulates spermatogenesis in the adult monkey. Endocrinology 123:1449–1455Google Scholar
  38. Wahlström T, Huhtaniemi I, Hovatta O, Seppälä M (1983) Localization of luteinizing hormone, follicle-stimulating hormone, prolactin, and their receptors in human and rat testis using immunohistochemistry and radioreceptor assay. J Clin Endocrinol Metab 57:825–830Google Scholar
  39. Wang C, Dahl KD, Leung A, Chan SY, Hsuch JW (1987) Serum bioactive follicle-stimulating hormone in men with idiopathic azoospermia and oligospermia. J Clin Endocrinol Metab 65: 629–633Google Scholar
  40. Weinbauer, Behre HM, Fingscheidt U, Nieschlag E (1991) 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 129:1831–1839Google Scholar
  41. WHO (1992) Laboratory manual for the examination of human semen and semen-cervical mucus interaction, 3rd edn. Cambridge University Press, CambridgeGoogle Scholar
  42. Yoon DJ, Golimbu M, Schinella R, Stein B, Sklar CA, David R (1987) Immunocytochemical localization of hFSH as an index of Sertoli cell function in the human testis. Acta Endocrinol 116:333–338Google Scholar
  43. Yoshinaga K, Nishikawa S, Ogawa M, Hayashi SI, Kunisada T, Fujimoto T, Nishikawa S (1991) Role of c-kit in mouse spermatogenesis: identification of spermatogonia as a specific site of c-kit expression and function. Development 113:689–699Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Tobias M. Böckers
    • 1
  • Eberhard Nieschlag
    • 2
  • Michael R. Kreutz
    • 3
  • Martin Bergmann
    • 1
  1. 1.Institute of AnatomyMünsterGermany
  2. 2.Institute of Reproductive MedicineUniversity of MünsterMünsterGermany
  3. 3.Institute of Medical PsychologyUniversity of MagdeburgGermany

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