Urocortin (UCN), a newly isolated peptide, has been found to play an important role mainly in female reproductive system. In order to investigate the effect of UCN on T-type calcium currents (I-Ca,I-T), exploring the mechanisms of UCN's role in male reproductive system, especially in acrosome reaction, we directly measured the I-Ca,I-T in mouse spermatogenic cells exposed to UCN using standard whole-cell patch-clamp recording technique. Our results showed that UCN reversibly inhibited the T-type Ca2+ currents in the cells in a concentration-dependent manner. The current density was inhibited by about 19% after exposure of the cells to UCN (0.1 mu M) for 5 min, from the control value of 6.75 +/- 1.17 to 5.26 +/- 0.82 pA/pF. UCN up-shifted the current voltage (I V) curve. Frequency-dependence of UCN's effects on I-Ca,I-T was also observed. Moreover, UCN at 0.1 mu M did not markedly affect the activation of I-Ca,I-T but shifted the inactivation curve of I-Ca,I-T to the left. The inhibitory effect of UCN on the T-type Ca2+ current was not affected by Astressin, the CRF receptor blocker. Since T-type calcium channels are a key component in acrosome reaction, our data suggest that UCN might be a significant factor in male reproductive action and a potential contraceptive agent. (c) 2005 Elsevier Inc. All rights reserved.