LEUKEMIA INHIBITORY FACTOR PRODUCED AT THE FETOMATERNAL INTERFACE STIMULATES CHORIONIC-GONADOTROPIN PRODUCTION - ITS POSSIBLE IMPLICATION DURING PREGNANCY, INCLUDING IMPLANTATION PERIOD

We investigated the role of leukemia inhibitory factor (LIF) at the im plantation site of human embryos. The first trimester decidual tissue produced higher levels of LIF than chorionic tissue, but the decidua p roduced much smaller amounts of interleukin-6 (IL-6) than the chorion in vitro, as determined by enzyme-linked immunosorbent assay. The reve rse transcription-polymerase chain reaction and immunohistochemical an alysis revealed the expression and localization, on the trophoblasts, of glycoprotein 130 (gp130), an IL-6 signal transducer receptor compon ent shared by the cytokines such as LIF and IL-6. Trophoblasts stimula ted by recombinant LIF (rLIF) produced CG titer at the amount similar to that induced by rIL-6. Recombinant LIF-induced CG production was si gnificantly blocked by anti-gp130 antibody but not by anti-IL-6 recept or antibody, whereas rIL-6-induced CG was completely blocked by both a ntibodies. Recombinant LIF- and rIL-6-induced CG productions were both significantly blocked by genistein, a tyrosine kinase inhibitor, sugg esting an involvement of tyrosine kinase in gp130-mediated CG producti on. Since CG is capable of stimulating trophoblast growth and differen tiation as well as placental metabolism, LIF produced at the fetomater nal interface are considered to stimulate the trophoblasts to produce CG, which may contribute to the maintenance of the placental functions and embryonal growth.