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The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 2 811-817
Copyright © 2001 by The Endocrine Society

Original Studies

Endothelins Enhance Prostaglandin (PGE2 and PGF2{alpha}) Biosynthesis and Release by Human Luteal Cells: Evidence of a New Paracrine/Autocrine Regulation of Luteal Function

Fiorella Miceli, Francesca Minici, Marina Garcia Pardo, Pierluigi Navarra, Caterina Proto, Salvatore Mancuso, Antonio Lanzone and Rosanna Apa

Departments of Obstetrics and Gynecology (Fi.M., Fr.M., M.G.P., S.M., R.A.) and Pharmacology (P.N.), Università Cattolica del Sacro Cuore, 00168 Rome, Italy; and OASI Institute for Research (C.P., A.L.), 94018 Troina, Italy

Address all correspondence and requests for reprints to: Rosanna Apa, M.D., Department of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy. E-mail: krimisa{at}libero.it

We have previously shown that endothelin-1 (ET-1) is normally found in human luteal cells, where it is able to significantly inhibit both basal and hCG-induced progesterone production. To further expand our comprehension of the 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 and ET-3; PGF2{alpha} and PGE2 were assayed in the culture medium to investigate whether ETs also influence cyclooxygenase activity in these cells. We found that both ETs are able to significantly stimulate PGF2{alpha} and PGE2 release in a dose- and time-dependent manner. ET-1 was always more effective than ET-3. Experiments with two endothelin receptor antagonists (the BQ485 and BQ788 compounds, which block the ET-A and ET-B receptors, respectively) showed that the two endothelins induce PG production through different 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 also able to influence progesterone production, the present new data suggest an interesting interplay among progesterone, PGs, and ETs in the control of corpus luteum physiology.




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