Pregnancy associated increase in differentiation-stimulating factor (D-factor)/leukemia inhibitory factor...

Differentiation-stimulating factor (D-factor)/leukemia inhibitory factor (LIF) is known to have multiple biological activities besides induction of differentiation of mouse myeloid leukemia M1 cells. Little is known about how its activities are regulated in vivo, but it has been suggested to play a regulatory role in the mechanisms involved in development of mice. In this study, we found that a single class of D-factor-binding substance is present in normal mouse serum and that it increases transiently in the late stage of pregnancy. It inhibits the induction of differentiation of mouse myeloid leukemic M1 cells by D-factor by blocking the binding of this factor to the cells. It is a heat-labile protein with an apparent molecular weight of 130,000-150,000. The binding of 125I-D-factor to the substance is specific since it was inhibited by excess unlabeled D-factor, but not by interleukin 6 or interferon gamma. The dissociation constant of the binding substance for mouse D-factor in normal mouse serum is 6.6-9.4 nM. In the late stage of pregnancy, the amount of the D-factor-binding substance in the serum apparently increases about 30-fold. These results suggest that the D-factor-binding substance regulates the activity of D-factor during embryonic development of mice.