Differential involvement of adrenal and gonadal steroids in anterior and intermediate pituitary pro-opiomelanocortin mRNA expression induced by the endogenous benzodiazepine, octadecaneuropeptide, in adult male rats

The involvement of the endogenous benzodiazepine, octadecaneuropeptide (ODN ), in the regulation of proopiomelanocortin (POMC) mRNA expression at the p ituitary level, and the influence of adrenal and gonadal steroids, have bee n studied using a quantitative in situ hybridization technique. I.c.v. inje ction of ODN (4 mu g/ kg) in sham-operated rats induced a 17 and 7% decreas e in the POMC mRNA expression in anterior and intermediate pituitary lobes respectively. To determine the reciprocal involvement of adrenal and gonada l steroids in this regulation, animals were adrenalectomized and/or castrat ed. Adrenalectomy significantly increased POMC mRNA expression by 48% at th e anterior pituitary level, but induced a 10% decrease of hybridization sig nal at the intermediate pituitary lobe (vs control sham-operated). Adrenal ablation reversed the effect induced by ODN and increased POMC mRNA express ion at the anterior and intermediate pituitary levels by 60 and 10% respect ively, compared with control sham-operated. By contrast, castration, which produced a decrease in POMC mRNA in the anterior pituitary and an increase in the intermediate lobe, did not modify the negative influence of ODN obse rved in sham-operated animals. When rats were adrenalectomized and castrate d, the adrenalectomy influence was predominant at the anterior pituitary le vel, since ODN increased significantly the hybridization signal (+68% vs co ntrol sham-operated), while the castration influence was predominant at the intermediate pituitary level, since ODN induced an 11% decrease in POMC mR NA signal compared with control sham-operated. These studies indicate that, in vivo, the decrease in POMC mRNA expression in the anterior and intermed iate pituitary induced by an endogenous benzodiazepine is differently modul ated by adrenal and gonadal steroids, with a predominant influence of adren al steroids at the anterior pituitary level and gonadal steroids at the int ermediate pituitary level.