Direct effect of testosterone and its 5alpha-reduced metabolites on pituitary LH and FSH release in vitro: change in pituitary responsiveness to hypothalamic extract.

A continuous flow incubation (perifusion) system was used to examine the effect of testosterone (T) and three of its 5alpha-reduced metabolites, dihydrotestosterone (DHT), 5alpha-androstane-3alpha, 17beta-diol (3alpha-Adiol) and its 3beta-epimer (3beta-Adiol) on LH and FSH release, induced by hypothalamic extract (HE). In the absence of steroids, successive identical pulses of HE, of 10 min duration each, administered at hourly intervals over a 8-hr period, caused highly reproducible release of LH and FSH. In experimental perifusions, the amounts of LH and FSH released in response to standard 10-min pulses of HE administered at hourly intervals during the continuous infusion of steroid for 4-6 hr were compared with the responses of the same pituitaries to the standard test pulses of HE given before the start of the steroid infusion and after its cessation. All the androgens tested altered pituitary responsiveness. At the 0.1 and 1.0 mug/ml dose level there were differences between the steroids in the way they influenced the responsiveness of the pituitary overtime. Their effects at these two doses fell into three categories depending on whether there was initially: 1) an augmentation of HE induced LH release (T and 3beta-Adiol), 2) augmentation of both FSH and LH release (DHT), OR 3) NO AUGMENTATION IN THE RELEASE OF EITHer gonadotrophin (3alpha-Adiol). All the androgens ultimately suppressed pituitary responsiveness to HE and all were associated with changes in the ratios of LH and FSH released. When the dose of T and 3 beta-Adiol was raised to 10 mug/ml or that of DHT lowered to 0.01 mug/ml the initial stimulatory phase was not seen. Epitestosterone, the biologically inactive epimer of T, did not alter the responsiveness of the pituitary of HE.