Characterization of the Mitogen-regulated Protein (proliferin) Receptor

Mitogen-regulated protein (MRP/PLF; also called proliferin) is a member of the PRL-GH family expressed by the placenta in mid-gestation. This report describes an MRP/PLF receptor in uterine membrane preparations from pregnant mice. Peak receptor activity occurred at 11 days of gestation with a dissociation constant of 6 x 10(-10) M and maximal binding capacity of 86 fmole MRP/PLF/mg membrane protein. PRL, PL-I, and mannose-6-phosphate did not compete for binding, and GH competed weakly only at high concentrations. Primary cells cultured from uteri taken at days 8-11 of gestation responded to MRP/PLF with increases in DNA synthesis. Uterine cells from later stages of gestation did not respond to MRP/PLF. This is the first reported evidence of a function mediated by MRP/PLF and suggests a role for this protein in maternal-fetal interactions during reproduction. Thus, it seems that MRP/PLF is a placentally derived growth factor, which stimulates proliferation in the uterus in a developmentally defined period to coordinate uterine growth with fetal development.