Interleukin-1 beta (IL-1 beta) is a modulator of human luteal cell steroidogenesis: Localization of the IL type I system in the corpus luteum

The present investigation examined the effect of interleukin-1 beta (IL-1 b eta) on progesterone production by human luteal cells and the expression an d localization of the IL-1 system in the human corpus luteum (CL). Luteal c ells were isolated from corpora lutea collected throughout the luteal phase . After dispersion, luteal cells were treated with a panel of monoclonal an tibodies directed to leukocyte-specific molecules. The leukocytes were isol ated with immunomagnetic beads. Leukocyte-free luteal cells exhibited great er steroidogenic responsiveness to hCG toward the end of the luteal phase. The treatment of mixed luteal cells (total luteal cells) with IL-1 beta inh ibited by 60% hCG-stimulated progesterone production. Interestingly, the tr eatment of leukocyte-free luteal cells with IL-1 beta did not affect proges terone production. In addition, the treatment of mixed luteal cells with mo noclonal 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 I L-1 receptor antagonist were localized by immunohistochemistry in both soma tic and immune cells of the CL. Flow cytometric analysis indicated that bot h nonleukocyte luteal cells and leukocyte-luteal cells exhibited IL-1Rt-I p ositive cells, representing 56% and 31% of the total luteal cells, respecti vely. However, 13% of nonleukocyte luteal cells did not express IL-1Rt-I. N orthern 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 mess enger ribonucleic acid. We conclude that 1) luteal leukocytes have an inhib itory effect on hCG-stimulated progesterone production; 2) IL-1 beta inhibi ts hCG stimulated progesterone production only in mixed luteal cell culture s, 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 sugges ts a functional intraovarian role for IL-1 beta in CL physiology.