The mode of FSH actions within the testis was studied in immature hypophysectomized male rats by treatment with recombinant human FSH (recFSH, Org 32489). To elucidate the involvement of Leydig cells and androgens in the maintenance of spermatogenesis in FSH-treated hypophysectomized 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 given one i.p. injection of vehicle or EDS and, 4 days later, they were implanted with osmotic minipumps releasing either 0·9% (w/v) NaCl 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-pretreated 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 testosterone from 0·12 ± 0·02 to 0·22 ± 0·03 nmol/l ( P <0·05) when the rats were treated with recFSH. EDS alone did not affect testicular testosterone but, when combined with recFSH, it totally abolished the stimulatory effect of FSH on testosterone. Testicular binding of ¹²⁵ I-labelled iodo human chorionic gonadotrophin (hCG) and ¹²⁵ I-labelled iodo recFSH 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, FSH increased its own receptors only in animals not treated with EDS.

Histological analysis of the testes revealed that the diameters of the seminiferous tubules increased from 115 ± 6·1 to 160 ± 7·2 μm ( P <0·05) with recFSH, and a comparable increase was observed when EDS treatment preceded that of recFSH (143 ± 1·5 μm, P <0·05 vs. controls). Quantification of the spermatogenic cells indicated that recFSH supported the progression of spermatogenesis, as shown by increased number of meiotic and haploid spermatogenic cells ( P <0·05). In all EDS-treated animals, spermatogenesis was severely disturbed and only a few spermatids were seen.

In conclusion: (1) these results further support the suggestion that FSH has indirect stimulatory effects on Leydig cell function, (2) the completion of meiosis and spermiogenesis are supported by FSH, the effect of which is enhanced by the presence of Leydig cells, suggesting its dependence on androgens, and (3) we show for the first time that FSH is able to stimulate its own receptors only in the presence of Leydig cell-derived factors, probably androgens.

Journal of Endocrinology (1994) 141, 449–457