Endothelins enhance prostaglandin (PGE(2) and PGF(2 alpha)) biosynthesis and release by human luteal cells: Evidence of a new paracrine/autocrine regulation of luteal function

We have previously shown that endothelin-1 (ET-1) is normally found in huma n luteal cells, where it is able to significantly inhibit both basal and hC G-induced progesterone production. To further expand our comprehension of t he possible roles of endothelins (ETs) in luteal physiology, in this study we used primary cultures of luteal cells exposed to graded doses of ET-1 an d ET-3; PGF(2 alpha) and PGE(2) were assayed in the culture medium to inves tigate whether ETs also influence cyclooxygenase activity in these cells. W e found that both ETs are able to significantly stimulate PGF(2 alpha) and PGE(2) release in a dose- and time-dependent manner. ET-1 was always more e ffective than ET-3. Experiments with two endothelin receptor antagonists (t he BQ485 and BQ788 compounds, which block the ET-A and ET-B receptors, resp ectively) showed that the two endothelins induce PG production through diff erent receptors and signaling pathways. In conclusion, here we demonstrate the ability of ETs to influence PG synthesis and release from human luteal cells. As PGs are deeply involved in corpus luteum activity, and ETs were a lso able to influence progesterone production, the present new data suggest an interesting interplay among progesterone, PGs, and ETs in the control o f corpus luteum physiology.