Human Reproduction, Vol 13, 2425-2429, Copyright © 1998 by Oxford University Press
R Apa, F Miceli, D de Feo, ML Mastrandrea, S Mancuso, M Napolitano and A Lanzone
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.
ARTICLES
Endothelin-1 inhibits basal and human chorionic gonadotrophin- stimulated progesterone production
Department of Obstetrics and Gynecology, Universita Cattolica S.Cuore, Roma, Italy.
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