Endothelins enhance prostaglandin (PGE(2) and PGF(2alpha)) 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 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; PGF(2alpha) and PGE(2) 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 PGF(2alpha) and PGE(2) 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.
Miceli
F
F
Department of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
Minici
F
F
Garcia Pardo
M
M
Navarra
P
P
Proto
C
C
Mancuso
S
S
Lanzone
A
A
Apa
R
R
D000959:Antihypertensive Agents / Q000494:pharmacology; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000242:Cyclic AMP / Q000494:pharmacology; D015237:Dinoprost / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D019334:Endothelin-3 / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007700:Kinetics; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011374:Progesterone / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000959:Antihypertensive Agents; D006063:Chorionic Gonadotropin; D019332:Endothelin-1; D019334:Endothelin-3; D009842:Oligopeptides; D010880:Piperidines; C086539:BQ 788; D011374:Progesterone; D015237:Dinoprost; D000242:Cyclic AMP; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate