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Trophoblast-Derived Interleukin-6 (IL-6) Regulates Human Chorionic Gonadotropin Release through IL-6 Receptor on Human Trophoblasts^*

ERIKO NISHINO, NOBORU MATSUZAKI, KAZUO MASUHIRO, TAKASHI KAMEDA, TAKESHI TANIGUCHI, TETSU TAKAGI, FUMITAKA SAJI and OSAMU TANIZAWA

Department of Obstetrics and Gynecology, Osaka University Medical School, 1–1-50 Fukushima Fukushima-ku, Osaka 553, Japan

We examined the capacity of trophoblast-derived interleukin-6 (IL-6) to stimulate secretion of placental hormones, including hCG. IL-6 stimulated hCG secretion by trophoblasts to a level similar to that stimulated by a GnRH analog. The analog, however, released hCG by an IL-6-independent mechanism because PM-1, a monoclonal antibody specific for IL-6 receptors (R), failed to block GnRH-mediated responses, but completely blocked IL-6-mediated hCG secretion, suggesting the existence of two distinct regulatory pathways for hCG release. Immunohistochemical analysis with another IL-6-R-specific antibody, MT-18, showed that IL-6-R was located only on the trophoblast layer of the placenta. Our data revealed the existence of a local regulatory network by which trophoblastderived IL-6 interacts with IL-6-R on the trophoblasts, resulting in hCG release. Thus, two different regulatory networks, an IL-6 and IL-6-R system and a GnRH and GnRH-R system, regulate hCG release by human trophoblasts independently.

^* This work was supported by Grants-in-Aid for Scientific Research 63570779, 63480367, and 01570930 from the Ministry of Education, Science, and Culture, Tokyo, Japan.

To whom all correspondence and requests for reprints should be addressed.

Received November 29, 1989.

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