Cell Journal (Yakhteh)
Volume:7 Issue: 2, 2005

The principal roles of the cyclic nucleotides in regulating sperm functions are well established, but the factors controlling their generation and actions have not yet been entirely understood. In particular, specific roles for cyclic GMP (cGMP) in mammalian sperm are poorly understood. In this study, we have characterized comparatively the cAMP and cGMP signaling systems in ejaculated human sperm. Mean concentrations of cGMP (0.1 µM) were found to be 100-fold lower than those of cAMP in non-stimulated cells, and adenylyl cyclase (AC) activities predominated by far over guanylyl cyclase (GC) activities in both paniculate and soluble protein fractions. By different experimental approaches (photoaffinity labeling, cyclase assays, and immunoblotting), we provided evidence for the presence or absence of different factors involved in either cAMP or cGMP pathways; the factors present consisted of guanylyl cyclase-A, soluble guanylyl cyclase, and regulatory and catalytic subunits of cAMP-dependent protein kinase, while the absent ones included guanylyl cyclase-B, natriuretic peptide clearance receptor, neuronal nitric oxide synthase, and cGMP-dependent protein kinsae I. Functional studies showed that cGMP, at high concentrations, can enhance sperm protein tyrosine phosphorylation, but not serine phosphorylation of glycogen synthase kinase. This study reveals that human sperm are characterized by an exceptional predominance of cAMP signaling and indicates potential roles for cGMP.