Pituitary-gonadal axis before puberty: evaluation of testicular steroids in the male rat.

Abstract

The relationship previously observed by us between androgens and the secretion of FSH and LH in immature male rats was further investigated by a series of castration-replacement experiments. Rats orchidectomized at 26 days of age were treated twice-daily with subcutaneous injections of various steroid preparations, each at several dosage levels, for 7 days. A “physiologic dosage range” was projected for each preparation, on the basis of the steroid dose which would give seminal vesicle or ventral prostate weights comparable to uncastrated controls. Levels of serum FSH and LH were measured with specific double-antibody radioimmunoassays. Testosterone maintained suppression of both serum FSH and LH to near intact control levels at a dosage approximating the “physiological dosage range,” although LH was suppressed by a lower dose than was FSH. 5α-Dihydrotestosterone and 3α-androstanediol could suppress serum LH only at the “physiological dosage range”; serum FSH suppression appeared at higher doses. Fluoxymesterone, an orally active androgenic drug, could suppress neither serum FSH nor LH to control levels within the “physiological dosage range.” 3β-Androstanediol was ineffective over a dose range of 30–2000 µg/kg/day body wt with respect to stimulation of accessory organ weights and to gonadotropin suppression. Seminal vesicle weights were considerably heavier in testosterone-treated animals than in those administered 5α-dihydrotestosterone, 3α-androstanediol, or fluoxymesterone on a dose-for-dose basis, while ventral prostate weights were similar for all four steroids. A dosage of estradiol equal to 0.3% of the suppressive testosterone dose suppressed both serum FSH and LH, and significantly stimulated seminal vesicle weight; estradiol treatment was equally effective for serum FSH and LH suppression. Results indicated that (1) the physiological activity of androgens, as judged by their effects on accessory organs, does not correlate well with the suppression of gonadotropins; (2) testicular steroid secretion can account for the suppressed levels of gonadotropins seen at age 26 days, but (3) metabolism of these steroids is probably necessary for suppressive action, in view of the incomplete results with fluoxymesterone; (4) metabolism of testosterone to estrogen may in part be necessary for complete FSH control; (5) the further reduction of 5α-dihydrotestosterone to 3α-androstanediol does not change its biological activity, while conversion to 3β-androstanediol destroys activity.