Endothelin-1 inhibits basal and human chorionic gonadotrophin-stimulated progesterone production.
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.
Apa
R
R
Department of Obstetrics and Gynecology, Università Cattolica S.Cuore, Roma, Italy.
Miceli
F
F
de Feo
D
D
Mastrandrea
M L
ML
Mancuso
S
S
Napolitano
M
M
Lanzone
A
A
D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D004347:Drug Interactions; D019332:Endothelin-1 / Q000494:pharmacology*; D019334:Endothelin-3 / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008184:Luteal Cells / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis*
D006063:Chorionic Gonadotropin; D019332:Endothelin-1; D019334:Endothelin-3; D011374:Progesterone