In the female rat, ovulation is preceded by a marked increase in the release of the decapeptide, LHRH, culminating in a preovulatory LH surge, which coincides with a period of sexual receptivity. The decapeptide, LHRH, is processed by a zinc metalloendopeptidase EC 22.214.171.124 (EP24.15) that cleaves the hormone at the Tyr5-Gly6 bond. We have previously reported that the autoregulation of LHRH gene expression can also be mediated by its metabolite, LHRH-(1-5). Given the central function of LHRH in reproduction and reproductive behavior, we examined the role of the metabolite, LHRH-(1-5), in mediation of LHRH-facilitated reproductive behavior. Intracerebroventricular administration of LHRH-(1-5) facilitated sexual behavior responses, similar to those facilitated by the decapeptide LHRH, in ovariectomized estradiol-primed female rats. Furthermore, immunoneutralization of EP24.15 resulted in the inhibition of the LHRH-facilitated lordosis but had no inhibitory effects on LHRH-(1-5)-facilitated lordosis. The LHRH antagonist, Antide, was capable of inhibiting LHRH-facilitated lordosis, without affecting LHRH-(1-5)-facilitated lordosis. Collectively, these results suggest a role for LHRH metabolites in the facilitation of female receptive behavior in rats.
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