Studies on mitogen regulated protein (proliferin) during murine development

Mitogen regulated protein/proliferin (MRP/PLF) is a glycoprotein with a significant percentage of positional identity in sequence with the prolactin-growth hormone family of proteins. MRP/PLF is secreted by proliferating mouse embryo cell lines and by the mouse placenta.;I developed a radioimmunoassay to examine the temporal and the spatial distribution of MRP/PLF throughout the pregnancy of CF-1 mice. The results revealed the appearance of MRP/PLF in mouse maternal plasma on the eighth day of gestation. The concentration of MRP/PLF in mouse maternal plasma reached a peak (8-10 [mu]g/ml) between the tenth and eleventh days of gestation (mid-pregnancy) and declined thereafter. Examination of various pregnant mouse tissue extracts obtained at different days in gestation revealed the presence of MRP/PLF in the placenta at a peak level (40-50 pg/[mu]g protein) between the ninth and thirteenth days of gestation; this level declined thereafter. The temporal distribution of MRP/PLF was associated with placental growth.;Other investigators have shown that MRP/PLF secreted by a cultured Chinese hamster ovary (CHO) cell line transformed with an expression vector containing mouse MRP/PLF cDNA binds the mannose 6-phosphate receptor. To examine whether MRP/PLF is cleared from maternal plasma via the mannose 6-phosphate receptors, and to gain some understanding of the structure of the carbohydrate chain on MRP/PLF, we examined the ability of MRP/PLF from maternal CF-1 mouse blood to bind to the mannose 6-phosphate receptor.;The similarity of MRP/PLF structure with prolactin and with placental lactogens, together with the temporal distribution of MRP/PLF in mouse maternal blood, allows us to propose MRP/PLF as a placental hormone. The results in this dissertation also suggest that the rate of MRP/PLF clearance from the maternal circulation via the mannose 6-phosphate receptor is developmentally regulated, and the levels of MRP/PLF are not regulated by testosterone