EFFECTS OF RECOMBINANT HUMAN FSH IN IMMATURE HYPOPHYSECTOMIZED MALE-RATS - EVIDENCE FOR LEYDIG CELL-MEDIATED ACTION ON SPERMATOGENESIS

The mode of FSH actions within the testis was studied in immature hypo physectomized male rats by treatment with recombinant human FSH (recFS H, Org 32489). To elucidate the involvement of Leydig cells and androg ens in the maintenance of spermatogenesis in FSH-treated hypophysectom ized rats further, the recFSH treatment was given both alone and after destruction of Leydig cells with ethane-1,2-dimethane sulphonate (EDS ). Three days after hypophysectomy (at 31 days of age) the rats were g iven one i.p. injection of vehicle or EDS and, 4 days later, they were implanted with osmotic minipumps releasing either 0.9% (w/v) NaCI or 1 IU recFSH/day. Recombinant FSH alone increased testicular weights 2. 5-fold in 7 days (P<0.01). The effect of FSH was similar in EDS-pretre ated rats (P<0.01). Testicular testosterone increased from 6.5 +/- 1.6 to 16.9 +/- 5.3 (S.E.M.) pmol/g tissue (P<0.05) and serum testosteron e from 0.12 +/- 0.02 to 0.22 +/- 0.03 nmol/l (P<0.05) when the rats we re treated with recFSH. EDS alone did not affect testicular testostero ne but, when combined with recFSH, it totally abolished the stimulator y effect of FSH on testosterone. Testicular binding of I-125-labelled iodo human chorionic gonadotrophin (hCG) and I-125-labelled iodo recFS H was increased 2.5- and 2.1-fold respectively with recFSH treatment ( P<0.01). EDS, either alone or with FSH, abolished specific testicular hCG binding (P<0.01), but had no effect on that of recFSH. However, FS H increased its own receptors only in animals not treated with EDS. Hi stological analysis of the testes revealed that the diameters of the s eminiferous tubules increased from 115 +/- 6.1 to 160 +/- 7.2 mu m (P< 0.05) with recFSH, and a comparable increase was observed when EDS tre atment preceded that of recFSH (143 +/- 1.5 mu m, P<0.05 vs. controls) . Quantification of the spermatogenic cells indicated that recFSH supp orted the progression of spermatogenesis, as shown by increased number of meiotic and haploid spermatogenic cells (P<0.05). In all EDS-treat ed animals, spermatogenesis was severely disturbed and only a few sper matids were seen. In conclusion: (1) these results further support the suggestion that FSH has indirect stimulatory effects on Leydig cell f unction, (2) the completion of meiosis and spermiogenesis are supporte d by FSH, the effect of which is enhanced by the presence of Leydig ce lls, suggesting its dependence on androgens, and (3) we show for the f irst time that FSH is able to stimulate its own receptors only in the presence of Leydig cell-derived factors, probably androgens.