Endothelin-l (ET-1) is a peptide classically produced by endothelial cells
and known for its powerful vasoconstrictor activity, However, recent data s
uggest 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 ch
orionic gonadotrophin (HCG) (100 ng/ml), Both basal and HCG-induced progest
erone production were significantly reduced by ET-1 at all examined times w
hereas preincubation of luteal cells with BQ485 (10(-9)-10(-6) M), an ET-A
receptor antagonist, prevented the inhibitory effect of ET-1, Conversely, n
o 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-myrista
te-13 acetate (PMA) (100 ng/ml), an activator of protein kinase C. Inhibiti
on of progesterone synthesis by PMA was similar to that induced by ET-1 alo
ne. 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 pat
hway. Conversely, ET-3 was not able to influence human luteal steroidogenes
is.