Effects of progesterone on sperm function: mechanisms of action

Progesterone stimulates sperm functions, e.g. hyperactivation, acrosome rea ction, binding to oocyte zona pellucida and penetration rate into the hamst er oocyte. The physiological relevance of these effects has been shown usin g female genital tract fluids which modulate sperm function according to th eir progesterone content. Progesterone interacts with specific sperm bindin g sites that, unlike the classic nuclear receptors, are located on the plas ma membrane of the spermatozoon. Binding studies have revealed the presence of two classes of progesterone receptors in the human spermatozoon, one cl ass has an elevated affinity constant (nanomolar) and is specific for proge sterone, 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 secon ds) increase of the intracellular free calcium concentration, followed by a sustained rise lasting for several minutes (plateau phase). Both these cal cium transients are dependent upon entry of extracellular calcium. The natu re of the calcium channel that mediates the effects of progesterone is, cur rently, unknown. It has been postulated that it may be: (i) part of the pro gesterone receptor; (ii) voltage-dependent; or (iii) operated by second mes sengers following activation of the progesterone receptor. Progesterone als o modulates sperm function by stimulating a trypsin-like proteolytic activi ty, the biosynthesis of polyamine (putrescine and spermidine), phospholipas e A(2) activity and protein tyrosine kinase activity in the sperm cell. Rec ent studies have shown that chloride ion efflux is vital for progesterone t o promote the acrosome reaction. This effect is achieved by interaction wit h a sperm membrane receptor which resembles the neuronal GABA(A) receptor. Accordingly, GABA(A) receptors have been found in the spermatozoon plasma m embrane and GABA stimulates hyperactivation and promotes the acrosome react ion.