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Interleukin-1ß Stimulates Progesterone Production by in Vitro Human Luteal Cells: Evidence of a Mediatory Role of Prostaglandins

Departments of Obstetrics and Gynecology (F.Mic., A.T., F.Min., R.A.) and Department of Pharmacology (P.N.), Università Cattolica del Sacro Cuore, 00168 Rome, Italy; and OASI Institute for Research (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 investigated whether IL-1ß, a cytokine with an important role in ovarian physiology, is also involved in progesterone (P) synthesis in human luteal cells, and whether this effect is mediated via the cyclooxygenase (COX) pathway. Human luteal cells were cultured for 24 h in the presence of IL-1ß (0.01–10 ng/ml), given alone or in combination with human chorionic gonadotropin (100 ng/ml), indomethacin (1 µg/ml), or P (100 ng/ml). We observed a significant increase in prostaglandin (PG)release after IL-1ß treatment; the cytokine was more effective on PGE₂ than PGF₂ release. The effect of IL-1ß was abolished by human chorionic gonadotropin, which had no action on basal PG levels when given alone; in contrast, P reduced basal, but not IL-1ß-stimulated, PG production. Treatment with the human IL-1 receptor antagonist was associated with a decrease in both basal and IL-1ß-stimulated PG production. Moreover, IL-1ß induced a concentration-dependent increase in P production and release, an effect counteracted by the COX inhibitor indomethacin.

In conclusion, our data show the ability of IL-1ß to influence P secretion via the COX pathway, thereby suggesting a possible luteotropic role in human ovary based on an autocrine-paracrine mechanism.

Abbreviations: CL, Corpora lutea; COX, cyclooxygenase; hCG, human chorionic gonadotropin; IL-1ra, IL-1 receptor antagonist; P, progesterone; PG, prostaglandin.

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