Roles of the mitogen-induced proteins, mitogen regulated protein/proliferin and 24p3/uterocalin, during mouse development
Mitogens, serum and growth factors, induce the secretion of several proteins in cell cultures. Mitogen regulated protein/proliferin (MRP/PLF) is one such protein secreted from 3T3 cells 20 hours after the addition of fibroblast growth factor (FGF). 24p3/uterocalin is another protein induced 10 hours after FGF addition. When combined with cycloheximide, 24p3/uterocalin secretion is increased by 5 fold.;MRP/PLFs are glycoproteins, belonging to the prolactin-growth hormone family, expressed at high concentration during mid-gestation in the mouse placenta. MRP/PLFs are thought to stimulate angiogenesis in the placenta and the uterus, and stimulate uterine cell growth during mid-gestation. To further study the roles of these glycoproteins, recombinant MRP/PLFs were created, and expressed and purified in 293 human fetal kidney cells.;To provide insights into the potential regulation of uterine cell proliferation by MRP/PLFs, the profiles of the wet weight and DNA content of the uterus were characterized and found to have a positive correlation with the expression profile of MRP/PLFs. Direct examination of MRP/PLF stimulation by estradiol-17beta or progesterone in day 8 and 9 placental minced, organ cultures demonstrated no effect on secreted MRP/PLF levels. Purified MRP/PLFs were used to further study the uterine MRP/PLF receptor on primary uterine cell and organ cultures, and in an in vitro day 11 uterine membrane binding assay. No evidence of biological or binding activity to the uterine MRP/PLF receptor was detected.;Expression of 24p3/uterocalin was detected in the embryonic spine on gestational day 13 and shown to increase throughout gestation and over the life time of the mouse. In the liver 24p3/uterocalin mRNA levels were the highest in the late-gestational fetal liver and decreased within the first week after birth. The 24p3/uterocalin mRNA was also detected in the spleen of juvenile adults. The presence of 24p3/uterocalin mRNA in the fetal and juvenile liver and in the spine after birth appeared to correlate with hematopoiesis in these tissues and therefore it is hypothesized that 24p3/uterocalin may have a potential role in events related to both embryonic and adult hematopoiesis.