The role of androgens in the regulation of the hypothalamo-pituitary-testicular axis

The importance of discontinuous hormonal signals in endocrine communications is suggested by the ability of sustained hormonal signals to shut down, as opposed to stimulate, target cells, and by the observation that a change in pulse pattern can alter the response elicited. Serial sampling of the serum in catheterized, conscious, freely-moving rats was employed to investigate two aspects of pulsatility in the hypothalamo-pituitary-testicular feedback loop regulating reproduction in the adult male. First, in response to treatment with moderate to high doses of the testosterone (T) metabolite, dihydrotestosterone (DHT), pituitary responsiveness to exogenous LHRH was suppressed, and elevated post-castration mean LH levels declined due to a dose-dependent suppression of LH pulse frequency and amplitude. LH pulse amplitude was not suppressed by low dose DHT treatment, in spite of a dramatic suppression of pituitary responsiveness as measured, implying that a stimulatory androgenic influence on amplitude might be exerted upon hypothalamic LHRH release; blocking the endogenous opioid peptide system did not abolish this phenomenon. A stimulation of LH pulse amplitude was observed in orchidectomized rats given a low (sub-physiological) dose of T, and again, this effect was apparently mediated at a supra-pituitary site as pituitary responsiveness appeared unaltered at this T dose. These results suggest that the feedback regulatory actions of exogenous DHT, like those of T, are mediated at both the hypothalamus and the pituitary; this is consistent with the hypothesis that endogenous DHT mediates some of the negative and positive feedback effects of T in intact or T-treated orchidectomized animals. A second aspect of pulsatility was investigated in testes-intact rats. Fluctuations in serum T concentration are of a dual nature, reflecting both acute pulsatile bursts and prolonged episodes of testicular secretory activity, the precise pattern of which varies between and with