Trophoblast-derived interleukin-6 (IL-6) regulates human chorionic gonadotropin release through IL-6 receptor on human trophoblasts.

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 trophoblast-derived 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.