Steroid hormone progesterone released by cumulus cells surrounding the egg is a potent stimulator of human spermatozoa. It attracts spermatozoa towards the egg and helps them penetrate the egg’s protective vestments . Progesterone induces Ca 2+ influx into spermatozoa and triggers multiple Ca 2+ -dependent physiological responses essential for successful fertilization, such as sperm hyperactivation, acrosome reaction and chemotaxis towards the egg . As an ovarian hormone, progesterone acts by regulating gene expression through a well-characterized progesterone nuclear receptor . However, the effect of progesterone upon transcriptionally silent spermatozoa remains unexplained and is believed to be mediated by a specialized, non-genomic membrane progesterone receptor . The identity of this non-genomic progesterone receptor and the mechanism by which it causes Ca 2+ entry remain fundamental unresolved questions in human reproduction. Here we elucidate the mechanism of the non-genomic action of progesterone on human spermatozoa by identifying the Ca 2+ channel activated by progesterone. By applying the patch-clamp technique to mature human spermatozoa, we found that nanomolar concentrations of progesterone dramatically potentiate CatSper, a pH-dependent Ca 2+ channel of the sperm flagellum. We demonstrate that human CatSper is synergistically activated by elevation of intracellular pH and extracellular progesterone. Interestingly, human
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Progesterone activates the principal Ca 2+ channel of human sperm
Lishko, Polina V.; Botchkina, Inna L.; Kirichok, Yuriy
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, Volume 471 (7338)
Nature Publishing Group (NPG) – Mar 16, 2011
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