Effects of demethylzeylasteral and celastrol on spermatogenic cell Ca2+ channels and progesterone-induced sperm acrosome reaction

The male antifertility effect of a water-chloroform extract of Tripterygium wilfordii Hook. f. (GTW) and several monomers isolated from GTW has attracted worldwide interest. In the present study, the effects of two isolated monomers from GTW, demethylzeylasteral and celastrol, on the Ca2+ channels in mouse spermatogenic cells and on the sperm acrosome reaction were investigated by whole-cell patch-clamp recording and chlortetracycline staining methods, respectively. The results showed that demethylzeylasteral concentration-dependently and in a partially reversible manner inhibited the Ca2+ current in spermatogenic cells with an IC50 of 8.8 mug/ml. Celastrol decreased the Ca2+ current in the cells time-dependently and irreversibly. The changes in the activation and inactivation time constants of Ca2+ currents after application of these two compounds were also examined. Demethylzeylasteral increased both activation and inactivation time constants of Ca2+ currents, and celastrol had no significant effect on them. The two compounds also inhibited significantly the sperm acrosome reaction initiated by progesterone. These data suggest that inhibition of Ca2+ currents could be responsible for the antifertility activity of these compounds. (C) 2003 Elsevier Science B.V. All rights reserved.