EFFECT OF HYPOPHYSECTOMY ON PITUITARY ADENYLATE-CYCLASE ACTIVATING POLYPEPTIDE GENE-EXPRESSION IN THE RAT HYPOTHALAMUS

Pituitary adenylate cyclase activating polypeptide (PACAP) is a new me mber of the secretin/glucagon/vasoactive intestinal peptide (VIP) fami ly. It stimulates adenylate cyclase in cultured rat pituitary cells, w hich have PACAP-specific receptors and expression of pituitary hormone s. Therefore, PACAP is considered as a hypophysiotropic hormone. If so , there might be a feedback regulatory mechanism between pituitary hor mones and hypothalamic PACAP. In the present study, we used nuclear ru n-on and RNase protection assays to examine whether transcription of t he PACAP gene in the rat hypothalamus would change after hypophysectom y. PACAP levels in the hypothalamus were also determined by radioimmun oassay. The transcriptional rate of the PACAP gene and PACAP mRNA cont ent decreased 1 and 2 weeks after hypophysectomy. Radioimmunoassayable PACAP levels in the hypothalamus also decreased after hypophysectomy. These findings suggest that the reduced rate of PACAP gene transcript ion after hypophysectomy causes the decreased mRNA and peptide levels in the hypothalamus. Replacement with GH, PRL, T-4, corticosterone, an d testosterone significantly restored PACAP mRNA levels in hypophysect omized rats to those in control animals. The results suggest that feed back regulation takes place between pituitary hormones or pituitary-de pendent factors and hypothalamic PACAP.