Endogenous ACTH, not only a-melanocyte-stimulating hormone, reduces food intake mediated by hypothalamic mechanisms

摘要

ACTH and a-melanocyte-stimulating hormone (a-MSH) are both consecutively processed from proopiomelanocortin (POMC), which is synthesized in hypothalamic arcuate neurons innervating the paraventricular nuclei (PVN). POMC secretion/synthesis is regulated by energy availability. ACTH and a-MSH bind with equal affinity to melanocortin-4 receptors and elicit similar effects on signal transduction in-vitro. Endogenous a-MSH thus far is believed to be the major physiological agonist and to act in an anorexigenic manner. Until now, it was fully unknown whether endogenous ACTH is also involved in the regulation of appetite and food intake. In this study in rats, we now show that icv ACTH as well as a-MSH possess anorexigenic effects in the PVN or areas in close proximity in vivo and that the effect of ACTH is direct and not mediated via a-MSH. We investigated the roles of endogenous ACTH and a-MSH by PVN application of the respective antibodies under different physiological conditions. In satiated rats with high levels of ACTH and a-MSH in the PVN, antibody administration increased food intake and body weight gain; hungry animals were unaffected