Characterization of a prolactin-regulated gene in reproductive tissues using the prolactin receptor knockout mouse...

Prolactin (PRL) exerts pleiotropic physiological effects in various cells and tissues, although it is mainly considered as a regulator of reproduction and cell growth. Null mutation of the prolactin receptor (PRLR) gene leads to female sterility due to a failure of embryo implantation. Using this mouse model and the method of mRNA differential display, we identified PRL target genes that are regulated during the peri-implantation period. We characterized 1 among the 45 isolated genes, UA-3, which is regulated in the uterus as well as in the ovary during early pregnancy. This gene corresponds to a P311 mouse cDNA that was originally identified for its high expression in late-stage embryonic brain and adult cerebellum. We report here that UA-3 is present in numerous tissues as well as in ovary and uterus at the site of blastocyst apposition, and that its expression is hormonally regulated. Moreover, in situ hybridization reveals high expression in ovarian granulosa cells and in uterine epithelium. Recently, it has been suggested that P311 expression is tightly regulated at several levels by mechanisms that control cellular growth, transformation, motility, or a combination of these. Taken together, these results suggest that P311 could be involved in these processes during pregnancy, although its function remains to be clearly established.