Differential Effects of Testosterone and Its Metabolites on Gonadotrophin Secretion in the Intact Adult Male Rat

Abstract

The effects of testosterone, 5α-dihydrotestosterone (DHT), 5α-androstane-3α, 17β-diol (3α-diol), 5α-androstane-3β,17β-diol (3β-diol) and 17β-estradiol (E2) on the basal and the LHRH-induced secretion of LH and FSH were studied in the intact adult male rat under in vitro and in vivo conditions. When anterior pituitary glands were incubated in the presence of steroids, testosterone and DHT were found to exert dose-dependent modulatory effects on the gonadotrophin secretory responses to LHRH 10^-8 M: low concentrations of testosterone and DHT (10^-9 and 10^-8 M) increased the gonadotrophin responses to LHRH, whereas higher concentrations of testosterone and DHT (10^-6 to 10^-5 M) reduced the LH response to LHRH without affecting the FSH response. 3α-diol, 3β-diol and E2 did not influence the pituitary responsiveness to LHRH. Basal release of LH and FSH into the medium was not modified by the presence of any of the five steroids tested at concentrations from 10^-10 to 10^-5 M. When the various steroids were given subcutaneously to the intact adult male rat, testosterone, DHT, 3α-diol and E2 were found to exert short-term inhibitory effects on LH response to LHRH (100 ng/rat) from 0.5 to 8 h after their subcutaneous administration. A single injection of 50 µg testosterone reduced the LH-response to LHRH for 8 h, whereas higher doses of DHT or 3α-diol (500 µg) or repeated injections were needed to obtain the same inhibitory effects. 3α-diol was less effective than DHT, and 3β-diol did not show any effect on gonadotrophin secretion. The present data indicate that in the intact adult male rat: (a) testosterone and DHT can affect gonadotrophin secretion directly at the pituitary level; (b) dose-dependent stimulatory and inhibitory effects of testosterone and DHT can be observed on gonadotrophin response to LHRH, at least under in vitro conditions; (c) in vivo treatment with testosterone, DHT and 3α-diol partially inhibits the LH response to LHRH, testosterone being clearly more potent than DHT and 3α-diol, and 3β-diol being ineffective. Testosterone thus appears to be the main androgen involved in the regulation of LH secretion in the intact adult male rat.