TEMPORAL AND STAGE-SPECIFIC EFFECTS OF RECOMBINANT HUMAN FOLLICLE-STIMULATING-HORMONE ON THE MAINTENANCE OF SPERMATOGENESIS IN GONADOTROPIN-RELEASING-HORMONE ANTAGONIST-TREATED RAT

Despite considerable attention to the hormonal regulation of spermatogenesis, the role of FSH in adult mammals remains controversial. This is mainly due to the unavailability until recently of FSH preparations free of contaminating LH and discrepant results in various species. Using LH-free recombinant human FSK (rhFSH), we sought to determine if FSH is able to maintain spermatogenesis in rats in which both LH and FSH, but not other pituitary hormones, are markedly suppressed by GnRH-A treatment. Groups of five adult SD rats were given daily sc injections of vehicle, Nal-GIu-GnRH-A (1.25 mg/kg BW) or GnRH-A + 10 IU rhFSH for up to 4 weeks. In agreement with our previous report, GnRH-A treatment for 1 week led to a significant (P < 0.05) reduction in testis weight (26.6%) and in the number of specific germ cells involving preleptotene (27.7%) and pachytene spermatocytes (36.7%) and step 7 spermatids (30.3%) at stage VII of the seminiferous epithelial cycle. The number of advanced spermatids declined by 44.3%. Concomitant administration of rhFSH for 1 week resulted in a significant increase in testicular weight, tubular areas at stage VII-VIII, and in the absolute volumes of seminiferous tubules and their lumens compared to GnRH-A alone. Most importantly, FSH replacement to GnRH-A-treated rats fully attenuated the early (1 week) GnRH-A-induced reduction in germ cell numbers at stage VII as well as the number of advanced (steps 17-19) spermatids, and effectively prevented GnRH-A-induced reduction in the number of pachytene spermatocytes and step 7 spermatids for 2 weeks. In addition, FSH replacement to GnRH-A-treated rats was able to increase the number of B spermatogonia available for entry into meiosis and maintain the number of preleptotene spermatocytes throughout the treatment period. The observed beneficial effects of rhFSH an spermatogenesis in GnRH-A-treated rats are most likely not due to the stimulation of the Leydig cell function (via paracrine interaction between Sertoli and the Leydig cells), because FSH addition to GnRH-A had no discernible effect on intratesticular or plasma T levels, accessory organs weight, and the total volume of the Leydig cells when compared with GnRH-A alone. These results demonstrate a positive role and relative contribution of FSH on the maintenance of spermatogenesis in the adult rats and provide a basis for further studies directed toward the identification of modulatory factor(s), involved in the interaction between the target cell (Sertoli) and the stimuli and between Sertoli and germ cells, which in turn regulates the proliferation and differentiation of germ cells.