Endothelin-1: Expression and role in human corpus luteum

PROBLEM: Several recent data suggest an involvement of endothelin (ET)-1, a powerful vasoconstrictor peptide, in reproductive function. This study was designed to investigate the presence and role of ET-1 in human corpus lute um. METHOD OF STUDY: Purified luteal cells were incubated for different times w ith ET-1 or ET-3 alone or associated with human chorionic gonadotropin. In another set of experiments cells were treated with ET-1 and BQ485, an ET-A receptor antagonist, or with phorbol 12-myristate-13 acetate (PMA), an acti vator of protein kinase C. RESULTS: ET-1 reduced both basal and human chorionic gonadotropin-induced p rogesterone production at all examined times, similarly PMA inhibited basal progesterone synthesis. BQ485 prevented the inhibitory effect of ET-1, whi le no effect was observed with ET-3. Finally, ET-1 mRNA was detected in the luteal cells. CONCLUSION: ET-1 is expressed by human luteal cells and reduces basal and h uman chorionic gonadotropin-induced progesterone synthesis through the ET-A receptors and the protein kinase C pathway. Conversely, ET-3 does not affe ct luteal steroidogenesis.