TYROSINE KINASE INHIBITION REDUCES THE PLATEAU-PHASE OF THE CALCIUM INCREASE IN RESPONSE TO PROGESTERONE IN HUMAN SPERM

Progesterone (P) has previously been shown to induce a rapid increase in [Ca2+](i) as well as tyrosine phosphorylation of proteins in human spermatozoa. Both these effects are essential for induction of the acr osome reaction by P. We investigated a possible relationship between t he P-induced calcium increase and tyrosine kinase activation, by evalu ating the effect of the tyrosine kinase inhibitor genistein on these t wo effects, We found that preincubation with genistein abolished P-ind uced tyrosine phosphorylation of two sperm proteins of 97 and 75 kDa m olecular weight and significantly inhibited the plateau phase of P-ind uced [Ca2+](i), increase without affecting the peak phase, Conversely, the plateau phase was enhanced by the tyrosine phosphatase inhibitor Na3VO4. The effect of genistein was specific for P, since no inhibitio n was observed on the [Ca2+](i) increase induced by thapsigargin, an i nhibitor of endoplasmic Ca2+-ATPase previously shown to mobilize Ca2in spermatozoa. These results indicate that tyrosine kinase activation is involved in the generation of the plateau phase of Ca2+ influx ind uced by P, and suggest the possibility that two different pathways are involved in the induction of Ca2+ entry by P in human sperm.