The effect and possible mode of action of alpha-melanocyte-stimulating hormone on gonadotropin release in the ovariectomized rat: an in vivo and in vitro analysis.

This study was designed to examine the possible effects of alpha MSH on gonadotropin release. Injection of alpha MSH into the third ventricle of the brain and sampling at 5, 10, 15, 30, and 60 min postinjection produced a significant lowering of plasma LH, but not of FSH, in conscious ovariectomized (OVX) rats. The minimum effective dose was 1 microgram. This procedure did not affect plasma levels of LH or FSH in estradiol benzoate-primed, OVX rats. Multiple blood sampling every 10 min before and after intraventricular injection of alpha MSH (2 micrograms) produced a significant reduction in the area under the secretion curve of LH. Intravenous injection of alpha MSH had little effect; however, a slight lowering of plasma LH occurred in OVX rats after a 50-micrograms dose. The effect of alpha MSH on LH release was blocked by pretreatment of the animals with alpha-methyl-paratyrosine, an inhibitor of catecholamine synthesis, as well as by pretreatment with an iv injection of spiroperidol, a dopamine receptor blocker. The peptide failed to alter basal or K+-stimulated LHRH release from median eminence fragments of OVX rats incubated in vitro. Alpha MSH had no effect on LHRH-induced LH release in vivo and failed to alter the release of FSH and LH from hemipituitaries of OVX rats or dispersed cells from OVX, estradiol benzoate-primed rats in vitro. It is concluded that alpha MSH exerts an inhibitory effect on LH release by an action on the hypothalamus, probably via activation of the tuberoinfundibular dopaminergic system.