This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by WEINBAUER, G. F. Articles by NIESCHLAG, E. Search for Related Content PubMed PubMed Citation Articles by WEINBAUER, G. F. Articles by NIESCHLAG, E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB MENOTROPINS TESTOSTERONE

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)^*

Institute of Reproductive Medicine of the University D-4400 Munster, Germany

Address all correspondence and requests for reprints to: Prof. Dr. Eberhard Nieschlag, Institute of Reproductive Medicine of the University, Steinfurter Strasse 107, D-4400 Munster, Germany.

Abstract

The role of FSH in spermatogenesis was investigated in nonhuman primates depleted of testosterone by GnRH antagonist treatment. The GnRH antagonist antide (Nal-Lys; [N-acetyI-D-2-naphthyl-Ala¹,D-4-ch]oro-Phe²,D-pyrLdyl-Ala³, nicotinyl-Lys⁵,D-nicotinyl-Lys⁵,isopropyl-Lys⁸,D-Ala¹⁰]-GnRH) was used at a daily dose of 450 µg/kg to suppress endogenous gonadotropin and androgen production. Four groups of five cynomolgus monkeys (Macaca fascicularis) were subjected to the following treatment throughout a 16-week period: vehicle (group 1), GnRH antagonist (group 2), and GnRH antagonist plus human FSH (Fertinorm; 2 x 15 IU/day-animal; hFSH) during weeks 0-8 (group 3) or 8-16 (group 4). Testicular biopsies were performed before and after 4, 8, and 16 weeks of treatment. The tissue was analyzed by light microscopy and flow cytometry. Serum testosterone levels were suppressed into the range of ore hidec torn ized animals in all GnRH antagonist-treated groups. In the absence of hFSH, serum inhibin levels were also markedly lowered. Concomitant administration of hFSH attenuated the GnRH antagonist-induced reduction of testicular size, while delayed treatment with hFSH failed to restimulate testicular volume. Numbers of A-dark spermatogonia, the reserve stem cells, were not altered by any of the treatments. hFSH either fully maintained or increased the counts for A-pale spermatogonia (renewing stem cells). The development of pachytene spermatocytes and round and elongated spermatids was markedly reduced or inhibited by the GnRH antagonist within 6-18 weeks. In contrast, hFSH maintained these cell types at about 50% of baseline for 8 weeks. After 8 weeks of GnRH antagonist administration, hFSH stimulated A-pale spermatogonia and spermatocytes 2-to 3-fold with only minor effects on spermatid numbers. By means of flow cytometry, testicular cells were quantified according to DNA content. Within 8-16 weeks of GnRH antagonist treatment the percentage of 4C (mainly primary spermatocytes), lC (round spermatids), and ICC cells (elongated spermatids) had fallen from 65-75% to 5-25%. hFSH completely maintained the relative number of these cells, but failed to significantly restimulate the formation of ICC cells. From the present work in the GnRH antagonist-suppressed nonhuman primate model the following conclusions are drawn: 1) FSH exerts a stimulatory effect on testicular size and spermatogenesis; 2) the effects of FSH might be mediated via activation of the renewing testicular stem cells; 3) the ability of FSH alone to restart spermatogenesis is limited; and 4) simultaneous analysis of testicular biopsy material by light microscopy and flow cytometry provides a valuable approach for qualitative and quantitative assessment of spermatogenesis in the nonhuman primate. (Endocrinology 129: 1831–1839,1991)

Footnotes

^* This work was supported by the German Research Foundation (Ni-130/11-1, Project/Al).

Received November 3, 1991.

This article has been cited by other articles:

				D.R. Simorangkir, S. Ramaswamy, G.R. Marshall, C.R. Pohl, and T.M. Plant A selective monotropic elevation of FSH, but not that of LH, amplifies the proliferation and differentiation of spermatogonia in the adult rhesus monkey (Macaca mulatta) Hum. Reprod., July 1, 2009; 24(7): 1584 - 1595. [Abstract] [Full Text] [PDF]

				S. M. Ruwanpura, R. I. McLachlan, K. L. Matthiesson, and S. J. Meachem Gonadotrophins regulate germ cell survival, not proliferation, in normal adult men Hum. Reprod., February 1, 2008; 23(2): 403 - 411. [Abstract] [Full Text] [PDF]

				K. L. Matthiesson, R. I. McLachlan, L. O'Donnell, M. Frydenberg, D. M. Robertson, P. G. Stanton, and S. J. Meachem The Relative Roles of Follicle-Stimulating Hormone and Luteinizing Hormone in Maintaining Spermatogonial Maturation and Spermiation in Normal Men J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3962 - 3969. [Abstract] [Full Text] [PDF]

				K. L. Matthiesson and R. I. McLachlan Male hormonal contraception: concept proven, product in sight? Hum. Reprod. Update, July 1, 2006; 12(4): 463 - 482. [Abstract] [Full Text] [PDF]

				G. R. Marshall, S. Ramaswamy, and T. M. Plant Gonadotropin-Independent Proliferation of the Pale Type A Spermatogonia in the Adult Rhesus Monkey (Macaca mulatta) Biol Reprod, August 1, 2005; 73(2): 222 - 229. [Abstract] [Full Text] [PDF]

				A. Junaidi, C M. Luetjens, J. Wistuba, A. Kamischke, C.-H. Yeung, M. Simoni, and E. Nieschlag Norethisterone enanthate has neither a direct effect on the testis nor on the epididymis: a study in adult male cynomolgus monkeys (Macaca fascicularis) Eur. J. Endocrinol., April 1, 2005; 152(4): 655 - 661. [Abstract] [Full Text] [PDF]

				G. F. Weinbauer, C.-J. Partsch, M. Zitzmann, S. Schlatt, and E. Nieschlag Pharmacokinetics and Degree of Aromatization Rather Than Total Dose of Different Preparations Determine the Effects of Testosterone: A Nonhuman Primate Study in Macaca fascicularis J Androl, September 1, 2003; 24(5): 765 - 774. [Abstract] [Full Text] [PDF]

				J. Wistuba, A. Schrod, B. Greve, J. K. Hodges, H. Aslam, G. F. Weinbauer, and C. M. Luetjens Organization of Seminiferous Epithelium in Primates: Relationship to Spermatogenic Efficiency, Phylogeny, and Mating System Biol Reprod, August 1, 2003; 69(2): 582 - 591. [Abstract] [Full Text] [PDF]

				M. Haywood, N. Tymchenko, J. Spaliviero, A. Koch, M. Jimenez, J. Gromoll, M. Simoni, V. Nordhoff, D. J. Handelsman, and C. M. Allan An Activated Human Follicle-Stimulating Hormone (FSH) Receptor Stimulates FSH-Like Activity in Gonadotropin-Deficient Transgenic Mice Mol. Endocrinol., November 1, 2002; 16(11): 2582 - 2591. [Abstract] [Full Text] [PDF]

				R. I. McLachlan, L. O'Donnell, P. G. Stanton, G. Balourdos, M. Frydenberg, D. M. de Kretser, and D. M. Robertson Effects of Testosterone Plus Medroxyprogesterone Acetate on Semen Quality, Reproductive Hormones, and Germ Cell Populations in Normal Young Men J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 546 - 556. [Abstract] [Full Text] [PDF]

				T. Yazawa, T. Yamamoto, Y. Jin, and S.-i. Abe Follicle-Stimulating Hormone Is Indispensable for the Last Spermatogonial Mitosis Preceding Meiosis Initiation in Newts (Cynops pyrrhogaster) Biol Reprod, January 1, 2002; 66(1): 14 - 20. [Abstract] [Full Text]

				T. M. Plant and G. R. Marshall The Functional Significance of FSH in Spermatogenesis and the Control of Its Secretion in Male Primates Endocr. Rev., December 1, 2001; 22(6): 764 - 786. [Abstract] [Full Text] [PDF]

				H. Krishnamurthy, P. Suresh Babu, C. R. Morales, and M. R. Sairam Delay in Sexual Maturity of the Follicle-Stimulating Hormone Receptor Knockout Male Mouse Biol Reprod, August 1, 2001; 65(2): 522 - 531. [Abstract] [Full Text] [PDF]

				L. O’Donnell, A. Narula, G. Balourdos, Y.-Q. Gu, N. G. Wreford, D. M. Robertson, W. J. Bremner, and R. I. McLachlan Impairment of Spermatogonial Development and Spermiation after Testosterone-Induced Gonadotropin Suppression in Adult Monkeys (Macaca fascicularis) J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1814 - 1822. [Abstract] [Full Text]

				H. Krishnamurthy, N. Danilovich, C. R. Morales, and M. R. Sairam Qualitative and Quantitative Decline in Spermatogenesis of the Follicle-Stimulating Hormone Receptor Knockout (FORKO) Mouse Biol Reprod, May 1, 2000; 62(5): 1146 - 1159. [Abstract] [Full Text]

				R. Behr and G. F. Weinbauer Germ Cell-Specific Cyclic Adenosine 3',5'-Monophosphate Response Element Modulator Expression in Rodent and Primate Testis Is Maintained Despite Gonadotropin Deficiency Endocrinology, June 1, 1999; 140(6): 2746 - 2754. [Abstract] [Full Text]

				Y. Tokunaga, S. Imai, R. Torii, and T. Maeda Cytoplasmic Liberation of Protein Gene Product 9.5 during the Seasonal Regulation of Spermatogenesis in the Monkey (Macaca fuscata) Endocrinology, April 1, 1999; 140(4): 1875 - 1883. [Abstract] [Full Text]

				H. F. S. Huang, M.-T. Li, W. Giglio, R. Anesetti, J. E. Ottenweller, and L. M. Pogach The Detrimental Effects of Spinal Cord Injury on Spermatogenesis in the Rat Is Partially Reversed by Testosterone, but Enhanced by Follicle- Stimulating Hormone Endocrinology, March 1, 1999; 140(3): 1349 - 1355. [Abstract] [Full Text]

				S. S. Majumdar, S. J. Winters, and T. M. Plant A Study of the Relative Roles of Follicle-Stimulating Hormone and Luteinizing Hormone in the Regulation of Testicular Inhibin Secretion in the Rhesus Monkey (Macaca mulatta) Endocrinology, April 1, 1997; 138(4): 1363 - 1373. [Abstract] [Full Text] [PDF]