Effects of recombinant human FSH in immature hypophysectomized male rats: evidence for Leydig cell-mediated action on spermatogenesis

Abstract

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) 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-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 125I-labelled iodo human chorionic gonadotrophin (hCG) and 125I-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.(ABSTRACT TRUNCATED AT 250 WORDS)