Effects of progesterone on sperm function: mechanisms of action
Effects of progesterone on sperm function: mechanisms of action
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DOI：
10.1093/humrep/15.suppl_1.28
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发表时间：
2000-06-01
影响因子：
6.1
通讯作者：
D'Agata, R
中科院分区：
文献类型：
--
作者：
Calogero, AE;Burrello, N;D'Agata, R
孕酮刺激精子功能，例如超活化、顶体反应、与卵母细胞透明质酸结合和进入仓鼠卵母细胞的穿透率。这些效应的生理相关性已经通过使用女性生殖道液体显示出来，这些液体根据其孕酮含量调节精子功能。与经典的核受体不同，孕酮与位于精子质膜上的特异性精子结合位点相互作用。结合研究表明，在人类精子中存在两类孕酮受体，一类具有升高的亲和力常数（纳摩尔），对孕酮具有特异性，而另一类具有在微摩尔范围内的亲和力常数，并与其他羟化孕酮衍生物同样良好地结合。暴露于孕酮后，主要事件是细胞内游离钙浓度的快速（数秒内）增加，随后持续升高持续数分钟（平台期）。这两种钙瞬变都依赖于细胞外钙的进入。介导孕酮作用的钙通道的性质目前尚不清楚。据推测，它可能是：（i）孕酮受体的一部分;（ii）电压依赖性;或（iii）在孕酮受体激活后由第二信使操纵。孕酮还通过刺激精细胞中胰蛋白酶样蛋白水解活性、多胺（腐胺和亚精胺）的生物合成、磷脂酶A（2）活性和蛋白酪氨酸激酶活性来调节精子功能。最近的研究表明，氯离子流出是至关重要的孕酮，以促进顶体反应。这种作用是通过与精子膜受体相互作用实现的，该受体类似于神经元GABA（A）受体。因此，在精子质膜上发现了GABA（A）受体，GABA刺激精子超活化并促进顶体反应。
Progesterone stimulates sperm functions, e.g. hyperactivation, acrosome reaction, binding to oocyte zona pellucida and penetration rate into the hamster oocyte. The physiological relevance of these effects has been shown using female genital tract fluids which modulate sperm function according to their progesterone content. Progesterone interacts with specific sperm binding sites that, unlike the classic nuclear receptors, are located on the plasma membrane of the spermatozoon. Binding studies have revealed the presence of two classes of progesterone receptors in the human spermatozoon, one class has an elevated affinity constant (nanomolar) and is specific for progesterone, whereas the other class has an affinity constant in the micromolar range and binds equally well other hydroxylated progesterone derivatives. Following exposure to progesterone, the main event is a rapid (within seconds) increase of the intracellular free calcium concentration, followed by a sustained rise lasting for several minutes (plateau phase). Both these calcium transients are dependent upon entry of extracellular calcium. The nature of the calcium channel that mediates the effects of progesterone is, currently, unknown. It has been postulated that it may be: (i) part of the progesterone receptor; (ii) voltage-dependent; or (iii) operated by second messengers following activation of the progesterone receptor. Progesterone also modulates sperm function by stimulating a trypsin-like proteolytic activity, the biosynthesis of polyamine (putrescine and spermidine), phospholipase A(2) activity and protein tyrosine kinase activity in the sperm cell. Recent studies have shown that chloride ion efflux is vital for progesterone to promote the acrosome reaction. This effect is achieved by interaction with a sperm membrane receptor which resembles the neuronal GABA(A) receptor. Accordingly, GABA(A) receptors have been found in the spermatozoon plasma membrane and GABA stimulates hyperactivation and promotes the acrosome reaction.