Endothelin stimulates testosterone secretion by rat Leydig cells.
The present study was designed to evaluate the effects of endothelin (ET) on rat testicular steroidogenesis in vitro and the involvement of prostaglandins (PG) and extracellular calcium in its mechanism of action. To this purpose we examined the effects of ET-1 and ET-3 on basal testosterone secretion, the influence of ET-1 on PGE2 release, the interaction of ET-1 and ET-3 with human chorionic gonadotrophin (hCG) and the interference of indomethacin (an inhibitor of cyclooxygenase) and nifedipine (a calcium-channel blocker) in purified rat Leydig cells. The data indicate that ET-1 and ET-3 stimulate basal and hCG-induced testosterone production although the effects of ET-3 were less marked. In addition, a concomitant release of PGE2 was observed after exposure to ET-1. A synergistic interaction between ET-1 and hCG in stimulating testicular steroidogenesis was revealed. Indomethacin was ineffective in modifying ET-1 evoked testosterone output, while in the presence of nifedipine the stimulatory effect of ET-1 was completely abolished. Since it has been shown by others that ET-1 is produced by rat Sertoli cells and specific binding sites are present in Leydig cells, the results of our study indicate that such a peptide may be regarded as a new paracrine factor able to influence steroidogenesis in Leydig cells. The action of ET-1 requires the activity of voltage-operated Ca2+ channels, while PGE2 activation is not essential for its steroidogenic effect.
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Cattedra di Andrologia, Istituto di Clinica Medica V, Università La Sapienza, Rome, Italy.
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Fillo
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Romanelli
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D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007985:Leydig Cells / Q000187:drug effects*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D013739:Testosterone / Q000096:biosynthesis*
D006063:Chorionic Gonadotropin; D016232:Endothelins; D013739:Testosterone; D009543:Nifedipine; D015232:Dinoprostone; D007213:Indomethacin