PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE REGULATES RAT LEYDIG-CELL FUNCTION IN-VITRO

The present study was designed to evaluate the effects of both pituita ry adenylate cyclase-activating polypeptide (PACAP)-27 and PACAP-38 on testosterone, cAMP and prostaglandin E-2 (PGE(2)) production by purif ied rat Leydig cells. Because PACAP-38 shares homology with vasoactive intestinal peptide (VIP), the effects of VIP and both PACAP and VIP r eceptor antagonists on testicular steroidogenesis were also examined. PACAP-38 potentiated testosterone response to a low effective dose of human chorionic gonadotropin (hCG), while PACAP-27 was without effect. Furthermore, PACAP-38 amplified testosterone response to a wide conce ntration range of hCG until the submaximal dose. VIP evoked a dose-dep endent increase of both basal and hCG-induced testosterone production. PACAP potentiation of steroidogenesis was nullified in the presence o f a PACAP antagonist, but was not modified by a VIP antagonist. Moreov er, while VIP antagonist blunted testosterone response to VIP, PACAP a ntagonist was without effect. Increasing concentrations of PACAP-38 ev oked a dose-response enhancement of both cAMP and PGE, production. How ever, this fatty acid is not involved in PACAP activity, as a prostagl andin blocker indomethacin did not modify the effect of PACAP on stero idogenesis. Taken together these findings: (i) demonstrate that PACAP- 38 is able to activate both cAMP- and phosphatidylinositol-dependent m echanisms in Leydig cells, (ii) indicate that the peptide exerts an am plificatory action on testicular steroidogenesis stimulated by hCG and that this activity is receptor-mediated, as it is prevented by a PACA P receptor antagonist; (iii) predict the existence of specific PACAP r eceptors (type 1 binding sites) on Leydig cells.