THE REGULATION OF GONADOTROPIN-RELEASING HORMONE-INDUCED CALCIUM SIGNALS IN MALE-RAT GONADOTROPHS BY TESTOSTERONE IS MEDIATED BY DIHYDROTESTOSTERONE

The biological effects of testosterone (T) may be mediated directly by T or indirectly by its metabolites, dihydrotestosterone (DHT) and est radiol. The present study examined whether the metabolism of T is invo lved in the regulation of GnRH-induced Ca2+ signaling at the pituitary . In gonadotrophs from castrated rats, a significantly greater percent age of gonadotrophs demonstrated oscillatory Ca2+ responses to 100 nM GnRH than cells from intact rats (72% vs. 24%; P < 0.05). This increas e was prevented by the administration of T propionate (0.1 mg/kg day), DHT benzoate (2 mg/kg day,), estradiol benzoate (EB; 5 mu g/kg day), or the combination of the above doses of DHT benzoate and EB. In all c ases the proportion of gonadotrophs hom the steroid treated rats havin g oscillatory Ca2+ responses to 100 nM GnRH was between 21-25% (P > 0. 05, compared with intact rats). To assess the importance of T metaboli sm, intact male rats were treated with the aromatase inhibitor letrozo le (1 mg/kg day), the 5 alpha-reductase inhibitor finasteride (50 mg/k g day), or their respective vehicles for 7 days. Letrozole had no effe ct on GnRH-induced Ca2+ signals, serum LH concentrations, or ventral p rostate or testes weight. Finasteride treatment, however, mimicked the effects of castration, with significantly more gonadotrophs exhibitin g Ca2+ oscillations in response to 100 nM GnRH than gonadotrophs from the vehicle-treated group (71% vs. 20% respectively; P < 0.05). Finast eride also caused a significant (P < 0.05) decrease in prostatic weigh t and DHT concentration, but had no significant effect on either prost atic T or serum LH concentrations. These findings suggest that in the intact male rat, the effects of T on GnRH-induced Ca2+ signaling are p referentially mediated via DHT. The results of this study also show th at in the absence of androgens, estradiol may regulate GnRH-induced Ca 2+ signaling in the male rat pituitary.