Pituitary adenylate cyclase-activating polypeptide regulates rat Leydig cell function in vitro

Abstract

The present study was designed to evaluate the effects of both pituitary adenylate cyclase-activating polypeptide (PACAP)-27 and PACAP-38 on testosterone, cAMP and prostaglandin E 2 (PGE 2) production by purified rat Leydig cells. Because PACAP-38 shares homology with vasoactive intestinal peptide (VIP), the effects of VIP and both PACAP and VIP receptor 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 concentration range of hCG until the submaximal dose. VIP evoked a dose-dependent increase of both basal and hCG-induced testosterone production. PACAP potentiation of steroidogenesis was nullified in the presence of a PACAP antagonist, but was not modified by a VIP antagonist. Moreover, while VIP antagonist blunted testosterone response to VIP, PACAP antagonist was without effect. Increasing concentrations of PACAP-38 evoked a dose-response enhancement of both cAMP and PGE 2 production. However, this fatty acid is not involved in PACAP activity, as a prostaglandin blocker indomethacin did not modify the effect of PACAP on steroidogenesis. Taken together these findings: (i) demonstrate that PACAP-38 is able to activate both cAMP- and phosphatidylinositol-dependent mechanisms in Leydig cells; (ii) indicate that the peptide exerts an amplificatory action on testicular steroidogenesis stimulated by hCG and that this activity is receptor-mediated, as it is prevented by a PACAP receptor antagonist; (iii) predict the existence of specific PACAP receptors (type 1 binding sites) on Leydig cells.