Romanelli F, Fillo S, Isidori A, Conte D
Department of Medical Pathophysiology, University La Sapienza, Rome, Italy.
Neuropeptides. 1997 Aug;31(4):311-7. doi: 10.1016/s0143-4179(97)90064-0.
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 E2 (PGE2) production by purified rat Leyding 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 PGE2 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.
本研究旨在评估垂体腺苷酸环化酶激活多肽（PACAP）-27和PACAP-38对纯化的大鼠睾丸间质细胞睾酮、环磷酸腺苷（cAMP）和前列腺素E2（PGE2）生成的影响。由于PACAP-38与血管活性肠肽（VIP）具有同源性，因此还检测了VIP以及PACAP和VIP受体拮抗剂对睾丸类固醇生成的影响。PACAP-38增强了低有效剂量人绒毛膜促性腺激素（hCG）诱导的睾酮反应，而PACAP-27则无此作用。此外，PACAP-38增强了睾酮对宽浓度范围hCG直至亚最大剂量的反应。VIP引起基础和hCG诱导的睾酮生成呈剂量依赖性增加。在存在PACAP拮抗剂的情况下，PACAP对类固醇生成的增强作用消失，但不受VIP拮抗剂的影响。此外，虽然VIP拮抗剂减弱了睾酮对VIP的反应，但PACAP拮抗剂无此作用。PACAP-38浓度增加引起cAMP和PGE2生成呈剂量反应性增强。然而，这种脂肪酸不参与PACAP活性，因为前列腺素阻断剂吲哚美辛并未改变PACAP对类固醇生成的作用。综合这些发现：（i）表明PACAP-38能够激活睾丸间质细胞中cAMP和磷脂酰肌醇依赖性机制；（ii）表明该肽对hCG刺激的睾丸类固醇生成具有放大作用，且该活性是受体介导的，因为它可被PACAP受体拮抗剂阻断；（iii）推测睾丸间质细胞上存在特异性PACAP受体（1型结合位点）。
