Regulation of gonadotrophin-releasing hormone secretion by testosterone inmale sheep

In males, including the ram, testosterone, acting via its primary metabolit es oestradiol and dihydrotestosterone (DHT), suppresses circulating LH conc entrations. This effect is due primarily, although not totally, to decrease d frequency of gonadotrophin-releasing hormone (GnRH) pulses. The arcuate-v entromedial region (ARC-VMR) of the mediobasal hypothalamus and possibly th e medial preoptic area (mPOA) are sites at which oestradiol acts to suppres s GnRH, but the site of DHT action is not known. Given that native GnRH neu rones appear to contain few or no oestrogen or androgen receptors, the effe cts of testosterone metabolites probably are exerted by modulating activity of inhibitory interneurone systems such as beta-endorphin, dopamine, and g amma-aminobutyric acid (GABA). Although beta-endorphin clearly inhibits GnR H secretion, the observation that testosterone treatment during a long-day photoperiod reduced proopiomelanocortin (POMC) mRNA in the arcuate nucleus while coincidentally suppressing GnRH release indicates that beta-endorphin does not mediate the inhibitory effect of testosterone on GnRH. Activation of GABA, receptors in either the mPOA or ARC-VMR suppressed LH, whereas ac tivation of GABA, receptors in the ARC-VMR increased LH pulse amplitude. Th erefore, it is suggested that GABA acts in both regions to regulate LH. Whe reas testosterone affects GABA metabolism in the rat hypothalamus, its effe ct in the ram hypothalamus is yet to be determined. Testosterone treatment activated dopaminergic cells in the retrochiasmatic A15 area in the same an imals in which it suppressed POMC mRNA in the arcuate nucleus. This dopamin ergic system may partially mediate the negative feedback effect of testoste rone in the ram analogous to its role in partially mediating the negative e ffect of oestrogen in the ewe. Future studies must concentrate on determini ng how these and other putative inhibitory neuronal systems interact and ho w they in turn are regulated by environmental factors such as photoperiod.