Estradiol inhibits the effects of extracellular ATP in human sperm by a non genomic mechanism of action

Steroid hormones, beside their classical genomic mechanism of action, exert rapid, non genomic effects in different cell types. These effects are mediated by still poorly characterized plasma membrane receptors that appear to be distinct from the classic intracellular receptors. In the present study we evaluated the non genomic effects of estradiol (17βE(2)) in human sperm and its effects on sperm stimulation by extracellular ATP, a potent activator of sperm acrosome reaction. In human sperm 17βE(2) induced a rapid increase of intracellular calcium (Ca(2+)) concentrations dependent on an influx of Ca(2+) from the extracellular medium. The monitoring of the plasma membrane potential variations induced by 17βE(2) showed that this steroid induces a rapid plasma membrane hyperpolarization that was dependent on the presence of Ca(2+) in the extracellular medium since it was absent in Ca(2+) free-medium. When sperm were pre-incubated in the presence of the K(+) channel inhibitor tetra-ethylammonium, the 17βE(2) induced plasma membrane hyperpolarization was blunted suggesting the involvement of K(+) channels in the hyperpolarizing effects of 17βE(2). Extracellular ATP induced a rapid plasma membrane depolarization followed by acrosome reaction. Sperm pre-incubation with 17βE(2) inhibited the effects of extracellular ATP on sperm plasma membrane potential variations and acrosome reaction. The effects of 17βE(2) were specific since its inactive steroisomer 17αE(2) was inactive. Furthermore the effects of 17βE(2) were not inhibited by tamoxifen, an antagonist of the classic 17βE(2) intracellular receptor.