Comparative analysis between cyclic GMP and cyclic AMP signalling in human sperm.
The principal involvement of cyclic nucleotides in regulating sperm functions is well established, but the factors controlling their generation and actions have not yet been entirely resolved. In particular, specific roles for cyclic (c)GMP in mammalian sperm are poorly understood. In this study, we have characterized comparatively the cAMP and cGMP signalling systems in ejaculated human sperm. Mean concentrations of cGMP (0.1 micromol/l) were found to be 100-fold lower than those of cAMP in non-stimulated cells, and adenylyl cyclase (AC) activities predominate by far guanylyl cyclase (GC) activities in both particulate and soluble protein fractions. By different experimental approaches (photoaffinity labelling, cyclase assays, immunoblotting), we provide evidence for the presence (guanylyl cyclase-A, soluble guanylyl cyclase, regulatory and catalytic subunits of cAMP-dependent protein kinase) or absence (guanylyl cyclase-B, natriuretic peptide clearance receptor, neuronal nitric oxide synthase, cGMP-dependent protein kinase I) of different factors involved in either cAMP or cGMP pathways. 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 signalling and indicates potential roles for cGMP.
Willipinski-Stapelfeldt
Birthe
B
Institute for Hormone and Fertility Research at the University of Hamburg, Grandweg 64, D-22529 Hamburg, Germany.
Lübberstedt
Jörn
J
Stelter
Stephanie
S
Vogt
Karin
K
Mukhopadhyay
Amal K
AK
Müller
Dieter
D
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D008297:Male; D045265:Natriuretic Peptides / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015290:Second Messenger Systems / Q000502:physiology*; D013094:Spermatozoa / Q000502:physiology*
D045265:Natriuretic Peptides; D009419:Nerve Tissue Proteins; D000242:Cyclic AMP; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D000071679:Glycogen Synthase Kinase 3 beta; D017869:Cyclic GMP-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D006152:Cyclic GMP