Abstract
We have recently demonstrated that the inhibitory influence of the endogenous benzodiazepine receptor ligand octadecaneuropeptide (ODN) on gonadotropin-releasing hormone (GnRH) gene expression could be prevented by specific inhibitors of 3 beta-hydroxysteroid dehydrogenase and 5 alpha-reductase in adrenalectomized and castrated male rats, then suggesting an involvement of neurosteroids in the action of ODN on GnRH neurons. In order to study in detail the role of circulating steroids in the effect of ODN, we have evaluated the influence of adrenalectomy, castration and the combination of adrenalectomy and castration as well as the effect of dexamethasone administration in the response of GnRH gene expression to ODN in the male rat. The intracerebroventricular injection of ODN (4 h before sacrifice) produced a 36% decrease in the hybridization signal. Adrenalectomy induced a 21% decrease in GnRH mRNA levels. In the adrenalectomized rats, the injection of ODN increased by 11% the amounts of mRNA. As previously reported by our group, castration was found to enhance GnRH mRNA (15% over control values). In castrated animals, ODN produced an inhibitory effect in the hybridization signal which was of the same amplitude as that observed in sham-operated animals. Finally, the combination of adrenalectomy and castration resulted in a small but significant decrease in the hybridization signal, the values being intermediary between those observed after adrenalectomy and those obtained after castration. In these animals, ODN induced a 38% decrease in the amounts of GnRH mRNA. In animals that had been castrated and adrenalectomized, dexamethasone treatment during 4 days produced a 19% increase in hybridization signal. In these dexamethasone-treated animals, ODN produced the usual decrease (33%) in GnRH mRNA. These results demonstrate that gonadal hormones do not play a major role in the activation of the GABAA receptor complex by ODN. On the other hand, it clearly appears that glucocorticoids exert a tonic stimulatory influence on GnRH neuronal activity and are involved in the inhibitory effect of ODN. The mechanism of action of glucocorticoids, which seems complex since the influence of adrenalectomy on the ODN action can be prevented by orchidectomy, remains to be fully elucidated.