女性类固醇激素“孕酮”（黄体酮）是由卵巢和胎盘产生的，通过在一种已很好定性的“核孕酮受体”上发生的作用来支持受孕和胚胎形成。但由卵子周围的细胞释放的孕酮也在输卵管内刺激精子细胞，增强它们使卵子受精的能力，而孕酮这种作用的机制一直不清楚。现在，两个独立研究小组报告，孕酮能够强力激发精子鞭毛上的主要Ca2+通道CatSper。他们的数据表明，CatSper通道或一个直接相关的膜蛋白起一种新型孕酮受体的作用，该受体能调控孕酮在精子质膜层面上快速的、非基因组性质的效应。这些结果应能帮助确定孕酮和CatSper在精子中的生理作用，并且还可能导致新型非激素类避孕药的研发。封面图片：René Pascal/ Center of Advanced European Study and Research, Bonn。（生物谷Bioon.com）
生物谷推荐原文出处：
Nature doi:10.1038/nature09769
The CatSper channel mediates progesterone-induced Ca2+ influx in human sperm
Timo Strünker,1, 3 Normann Goodwin,1, 3 Christoph Brenker,1, 3 Nachiket D. Kashikar,1, 4 Ingo Weyand,2 Reinhard Seifert1 & U. Benjamin Kaupp1
In the oviduct, cumulus cells that surround the oocyte release progesterone. In human sperm, progesterone stimulates a Ca2+ increase by a non-genomic mechanism1, 2, 3. The Ca2+ signal has been proposed to control chemotaxis, hyperactivation and acrosomal exocytosis of sperm4, 5, 6, 7, 8. However, the underlying signalling mechanism has remained mysterious. Here we show that progesterone activates the sperm-specific, pH-sensitive CatSper Ca2+ channel9, 10, 11. We found that both progesterone and alkaline pH stimulate a rapid Ca2+ influx with almost no latency, incompatible with a signalling pathway involving metabotropic receptors and second messengers. The Ca2+ signals evoked by alkaline pH and progesterone are inhibited by the Cav channel blockers NNC 55-0396 and mibefradil. Patch-clamp recordings from sperm reveal an alkaline-activated current carried by mono- and divalent ions that exhibits all the hallmarks of sperm-specific CatSper Ca2+ channels10, 11. Progesterone substantially enhances the CatSper current. The alkaline- and progesterone-activated CatSper current is inhibited by both drugs. Our results resolve a long-standing controversy over the non-genomic progesterone signalling. In human sperm, either the CatSper channel itself or an associated protein serves as the non-genomic progesterone receptor. The identification of CatSper channel blockers will greatly facilitate the study of Ca2+ signalling in sperm and help to define further the physiological role of progesterone and CatSper.
