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Paracrine Regulation of Insulin-Like Growth Factor I (IGF-I) and IGF-II on Prostaglandins F₂ and E₂ Synthesis by Human Corpus Luteum in Vitro: A Possible Balance of Luteotropic and Luteolytic Effects

Departments of Obstetrics and Gynecology (A.P., M.F., P.E., M.F., C.A., M.S.) and Pharmacology (N.P.), Universitè Cattolica del Sacro Cuore, 00168 Rome; the Department of Experimental Medicine and Pathology, Universitè La Sapienza (N.M.), Rome; and OASI Institute for Research (L.A.), Troina, Italy

Address all correspondence and requests for reprints to: Apa Rosanna, M.D., Department of Obstetrics and Gynecology, Universitè Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy.

The existence of a complete intraovarian insulin-like growth factor (IGF) system replete with ligands, receptors, and binding proteins has been demonstrated as well as the ability of IGF-I to positively affect steroidogenesis in human granulosa cells. Furthermore, we recently showed that IGF-I and IGF-II stimulate progesterone secretion by human luteal cells. As the PGs, PGE₂ and PGF₂, are classically known to have luteotropic and luteolytic effects, we wanted to determine whether the IGFs could affect the human luteal phase by influencing the PG system. For this reason, human luteal cells were cultured for different times (12, 24, and 48 h) with IGF-I, IGF-II (10–100 ng/mL), and GH (100 ng/mL), and both PGs were assayed in the medium culture. We found that both IGF-I and IGF-II were able to stimulate PGE₂ synthesis in a time- and dose-dependent way, whereas they both inhibited PGF₂ production. GH, too, significantly reduced PGF₂ synthesis; this effect was IGF-I mediated because it was reverted by increasing dilutions of an anti-IGF-I antibody. On the contrary, no GH effect was observed on PGE₂ production. In conclusion, based on these data and on our previous results, we speculate that IGFs could influence luteal steroidogenesis through PG system.

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