Progesterone stimulates p42 extracellular signal-regulated kinase (p42erk) in human spermatozoa

Mitogen-activated protein kinases (MAPK), also known as extracellularsignal-regulated kinases (ERKs) are cytoplasmic and nuclearserine/threonine kinases involved in signal transduction of severalextracellular effectors. Recently, we have demonstrated that ERKs arepresent in spermatozoa and are involved in the regulation of the process ofcapacitation. We report here the effect of progesterone, a well-knowninducer of the acrosome reaction in mammalian spermatozoa, on theimmunolocalization, phosphorylation and activity of ERKs in capacitatedhuman spermatozoa. We demonstrated that short-term incubation ofspermatozoa with progesterone induces phosphorylation and activation ofERKs, resulting in redistribution of the proteins from the post-acrosomalregion to the equatorial segment within the sperm head. To investigate therole of ERKs on the biological effects of progesterone, we used the MAPKcascade inhibitor PD098059, which strongly inhibited progesterone-inducedactivation of ERK-2. This compound did not inhibit progesterone-inducedacrosome reaction, although it prevented redistribution of the enzyme tothe equatorial region of the sperm head. These results suggest that the twoprocesses, although temporally related, are independent. In conclusion, weprovide new insight into the signal transduction pathways involved in thenon- genomic action of progesterone in spermatozoa and suggest a possibleinvolvement of ERKs in the process of fertilization.