Endothelin-1 inhibits basal and human chorionic gonadotrophin-stimulated progesterone production

• Published in: Human reproduction (Oxford) Vol. 13; no. 9; pp. 2425 - 2429
• Main Authors: Apa, R, Miceli, F, de Feo, D, Mastrandrea, M L, Mancuso, S, Napolitano, M, Lanzone, A
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-09-1998
• Subjects: Biological and medical sciences; Cells, Cultured; Chorionic Gonadotropin - pharmacology; Drug Interactions; Endothelin-1 - pharmacology; Endothelin-3 - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Hormone metabolism and regulation; Humans; Luteal Cells - metabolism; Mammalian female genital system; Progesterone - biosynthesis; Vertebrates: reproduction; Human; Endothelin 1; Gene expression; In vitro; Ovarian hormone; Biological activity; Ovary; Luteal cell; Female genital system; Corpus luteum; Female; Steroidogenesis; Progesterone; Sex steroid hormone; Localization
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/13.9.2425

Endothelin-1 (ET-1) is a peptide classically produced by endothelial cells and known for its powerful vasoconstrictor activity. However, recent data suggest an involvement of ET-1 also in reproductive function. This study was designed to examine the possible presence and role of ET-1 in human luteal cells. Purified luteal cells were incubated for different times with ET-1 (10(-9)-10(-6) M) or ET-3 (10(-9)-10(-6)) alone or associated with human chorionic gonadotrophin (HCG) (100 ng/ml). Both basal and HCG-induced progesterone production were significantly reduced by ET-1 at all examined times whereas preincubation of luteal cells with BQ485 (10(-9)-10(-6) M), an ET-A receptor antagonist, prevented the inhibitory effect of ET-1. Conversely, no effect on progesterone synthesis was observed when ET-3 was added to the cultures. Luteal cells were then incubated for 24 h with phorbol 12-myristate-13 acetate (PMA) (100 ng/ml), an activator of protein kinase C. Inhibition of progesterone synthesis by PMA was similar to that induced by ET-1 alone. This study demonstrates that ET-1 negatively affects, at physiological concentrations, basal and HCG-induced progesterone synthesis. These effects seem to be exerted through the ET-A receptors and the protein kinase C pathway. Conversely, ET-3 was not able to influence human luteal steroidogenesis.