Signaling between the placenta and the uterus involving the mitogen-regulated protein/proliferins

The aim of this investigation was to examine signaling between the placenta and uterus during pregnancy. To do this, we determined the tissue messenge r RNA and protein levels of members of a glycopeptide hormone family known to stimulate the proliferation of uterine cells and related these levels to the growth of the uterus during pregnancy in the mouse. This hormone famil y is known as mitogen-regulated protein (MRP); alternatively proliferin (PL F). Three mrp/plf genes, plf1, mrp3 and mrp4, are expressed by the placenta with different developmental profiles. The major increase of about 4-fold in DNA content of the uterus occurs between days 9 and 14 when MRP/PLFs are present in the placenta. By contrast, the gestational changes in estradiol -17 beta levels in placental and uterine tissues and in circulation do not correlate with the period of uterine growth. The previously reported mitoge nic activity of the MRP/PLFs and their gestational profiles suggest that on e or more of these proteins stimulates uterine proliferation during gestati on. Evidence is also presented that expression of MRP3 and/or PLF1, but not MRP4, is negatively regulated by feedback from the uterus. Our results are consistent with the hypothesis that MRP/PLFs stimulate uterine proliferati on in vivo and that a uterine factor shuts off PLF1 and/or MRP3 synthesis i n the latter half of gestation.