PROGESTERONE STIMULATES P42 EXTRACELLULAR SIGNAL-REGULATED KINASE (P42(ERK)) IN HUMAN SPERMATOZOA

Mitogen-activated protein kinases (MAPK), also known as extracellular signal-regulated kinases (ERKs) are cytoplasmic and nuclear serine/thr eonine kinases involved in signal transduction of several extracellula r effecters. Recently, we have demonstrated that ERKs are present in s permatozoa and are involved in the regulation of the process of capaci tation. We report here the effect of progesterone, a well-known induce r of the acrosome reaction in mammalian spermatozoa, on the immunoloca lization, phosphorylation and activity of ERKs in capacitated human sp ermatozoa. We demonstrated that short-term incubation of spermatozoa w ith progesterone induces phosphorylation and activation of ERKs, resul ting in redistribution of the proteins from the post-acrosomal region to the equatorial segment within the sperm head. To investigate the ro le of ERKs on the biological effects of progesterone, we used the MAPK cascade inhibitor PD098059, which strongly inhibited progesterone-ind uced activation of ERK-2. This compound did not inhibit progesterone-i nduced acrosome reaction, although it prevented redistribution of the enzyme to the equatorial region of the sperm head. These results sugge st that the two processes, although temporally related, are independen t. In conclusion, we provide new insight into the signal transduction pathways involved in the non-genomic action of progesterone in spermat ozoa and suggest a possible involvement of ERKs in the process of fert ilization.