女性類(lèi)固醇激素“孕酮”（黃體酮）是由卵巢和胎盤(pán)產(chǎn)生的,，通過(guò)在一種已很好定性的“核孕酮受體”上發(fā)生的作用來(lái)支持受孕和胚胎形成,。但由卵子周?chē)募?xì)胞釋放的孕酮也在輸卵管內(nèi)刺激精子細(xì)胞，增強(qiáng)它們使卵子受精的能力,，而孕酮這種作用的機(jī)制一直不清楚?，F(xiàn)在，兩個(gè)獨(dú)立研究小組報(bào)告,，孕酮能夠強(qiáng)力激發(fā)精子鞭毛上的主要Ca2+通道CatSper,。他們的數(shù)據(jù)表明，CatSper通道或一個(gè)直接相關(guān)的膜蛋白起一種新型孕酮受體的作用,，該受體能調(diào)控孕酮在精子質(zhì)膜層面上快速的,、非基因組性質(zhì)的效應(yīng)。這些結(jié)果應(yīng)能幫助確定孕酮和CatSper在精子中的生理作用,，并且還可能導(dǎo)致新型非激素類(lèi)避孕藥的研發(fā),。封面圖片：René Pascal/ Center of Advanced European Study and Research, Bonn。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
