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Interleukin-1ß (IL-1ß) Is a Modulator of Human Luteal Cell Steroidogenesis: Localization of the IL Type I System in the Corpus Luteum¹

Institute of Maternal and Child Research, School of Medicine and Department of Obstetrics and Gynecology (P.K., A.C., O.C., M.V., L.D.), the Human Genetics Program, ICBM, School of Medicine (P.C.), University of Chile, Santiago, Chile; the Department of Obstetrics and Gynecology, University of Valencia (P.C.-C., C.S.), Valencia, Spain; and the Center for Research on Reproduction and Women’s Health and Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine (A.M.), Philadelphia, Pennsylvania 19104

Address all correspondence and requests for reprints to: Luigi Devoto M.D., University of Chile School of Medicine, P.O. Box 226–3, Santiago, Chile. E-mail: ldevoto{at}machi.med.uchile.cl

The present investigation examined the effect of interleukin-1ß (IL-1ß) on progesterone production by human luteal cells and the expression and localization of the IL-1 system in the human corpus luteum (CL). Luteal cells were isolated from corpora lutea collected throughout the luteal phase. After dispersion, luteal cells were treated with a panel of monoclonal antibodies directed to leukocyte-specific molecules. The leukocytes were isolated with immunomagnetic beads. Leukocyte-free luteal cells exhibited greater steroidogenic responsiveness to hCG toward the end of the luteal phase. The treatment of mixed luteal cells (total luteal cells) with IL-1ß inhibited by 60% hCG-stimulated progesterone production. Interestingly, the treatment of leukocyte-free luteal cells with IL-1ß did not affect progesterone production. In addition, the treatment of mixed luteal cells with monoclonal antibodies against IL-1 receptor type I (IL-1RtI) resulted in a 2.5-fold increase in the hCG-supported progesterone production. IL-1RtI and IL-1 receptor antagonist were localized by immunohistochemistry in both somatic and immune cells of the CL. Flow cytometric analysis indicated that both nonleukocyte luteal cells and leukocyte-luteal cells exhibited IL-1Rt-I positive cells, representing 56% and 31% of the total luteal cells, respectively. However, 13% of nonleukocyte luteal cells did not express IL-1Rt-I. Northern analysis demonstrated the presence of the 5.1-kb IL-1RtI messenger ribonucleic acid transcript in CL of different ages. RT-PCR indicated that both leukocyte-free luteal cells and luteal leukocytes express IL-1RtI messenger ribonucleic acid. We conclude that 1) luteal leukocytes have an inhibitory effect on hCG-stimulated progesterone production; 2) Il-1ß inhibits hCG-stimulated progesterone production only in mixed luteal cell cultures, indicating that leukocytes mediate the effect; 3) the somatic and immune cells of the CL are sites of action and expression of the IL-1 system; and 4) interaction between the steroidogenic and immune cells of the CL suggests a functional intraovarian role for IL-1ß in CL physiology.

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