The Hypothalamic Melanocortin System Stimulates the Hypothalamo-Pituitary-Adrenal Axis in vitro and in vivo in Male Rats

Abstract

α-Melanocyte-stimulating hormone (α-MSH) is an agonist, and agouti-related protein (Agrp) an endogenous antagonist at the melanocortin 3 and 4 receptors which are found in the central nervous system (CNS). We have examined the effect of α-MSH and Agrp on the hypothalamo-pituitary-adrenal (HPA) axis in vitro and in vivo in male rats. Intraparaventricular nuclear (iPVN) injection of [Nle4,D-Phe7]-α-MSH (NDP-MSH) (a long-acting α-MSH analogue) increased plasma adrenocorticotropic hormone (ACTH) (10 min post-injection: 25.0 ± 3.9 vs. saline 10.9 ± 2.0, p M) resulted in a 159 ± 23% increase in corticotropin-releasing hormone (CRH) release (p M) administered to hypothalamic explants resulted in a 161 ± 20% increase in CRH (p M) resulted in a 179 ± 31% increase in CRH release (p < 0.01) and 130 ± 9% increase in AVP release (p < 0.01) compared to basal, but there was no additive effect. This is the first report that both α-MSH and Agrp(83–132) stimulate the HPA axis. The combination of α-MSH and Agrp(83–132) has no additive effect in vitro and in vivo in male rats. These results suggest that there may be another receptor independent of the known melanocortin receptors at which Agrp is acting.