Centrally administered adrenomedullin increases plasma oxytocin level withinduction of c-fos messenger ribonucleic acid in the paraventricular and supraoptic nuclei of the rat

The effects of intracerebroventricular iev) administration of adrenomedulli n (AM) on plasma oxytocin (OXT), c-Fos protein (Fos), and c-fos messenger R NA (mRNA) in the paraventricular (PVN) and supraoptic nuclei (SON) of the r at were investigated using RIA for OXT, immunohistochemistry for Fos, and i n situ hybridization histochemistry for c-Fos mRNA. Central administration of AM caused a significant(-) increase in the plasma OXT level. Intracerebr oventricular administration of AM caused a marked induction of Fos-like imm unoreactivity (LI! in the PVN and in the dorsal parts of the SON. In the PV N and SON, OXT-LI cells predominantly exhibited nuclear Fos-LI in compariso n with arginine vasopressin-LI cells. In situ hybridization histochemistry revealed that the induction of c-fos mRNA in the PVN and SON was increased in a dose-related manner 30 min after icy administration of AM. This induct ion was reduced by pretreatment with the AM receptor antagonist. human AM-( 22-52)-NH2,. These results suggest that central AM is responsible for activ ating the neurosecretory cells in the PVN and SON via selective AM receptor s, and that AM stimulates the secretion of OXT by activating hypothalamic O XT-producing cells.