Gonadal steroid regulation of luteinizing hormone-releasing hormone and luteinizing hormone release in the male sheep

The purpose of this thesis was to investigate the role of testosterone (T) and its metabolites, estradiol (E) and dihydrotestosterone (DHT) in the regulation of LH release in male sheep. The first four studies examined the ability of T, E or DHT to inhibit LH release, and the sites at which they exert their effects. The final study examined the role of T in regulating seasonal changes of LH release in adult male and female sheep. A comparison between the effects of T and E on seasonal changes in LH release in males also was made. Five major conclusions were drawn from this work. Conclusions from the first four studies are, (1) prior administration of low T concentrations partially restores the negative feedback effects of abrupt increases of T on LH release in castrated male sheep, (2) E, but not DHT, rapidly reduces LH release in castrated male sheep by reducing LH pulse amplitude and frequency, (3) E acts directly on the anterior pituitary gland to rapidly reduce responsiveness to LHRH, not by rapidly reducing LHRH release, and (4) tyrosine hydroxylase-containing neurons of A14 and A15 are activated concomitant with T-induced suppression of LH release. The conclusion from the final study is (5) neuroendocrine mechanisms regulating seasonal changes in LH release are sexually differentiated. Seasonal changes of LH release in T-treated males also are more pronounced than in E-treated males. The results of these studies suggest the following model. A pulse of T released from the testes is metabolized to E. E rapidly reduces LH release by acting on the anterior pituitary gland to rapidly reduce pituitary responsiveness to LHRH, not by rapidly reducing LHRH release. The differential effects of T and E on seasonal changes in mean LH concentrations suggest other factors, including T or DHT, also regulate LHRH release. These factors may reduce LHRH release by activating tyrosine hydroxylase-containing neurons of A14 and A15.