Prolactin receptor and uterine milk protein expression in the ovine endometrium during the estrous cycle and pregnancy

Lactogenic hormones regulate epithelial proliferation, differentiation, and function in a variety of epitheliomesenchymal organs. During pregnancy, th e ovine uterus is a potential site for endocrine and paracrine actions of l actogenic hormones in the form of pituitary prolactin (PRL) and placental l actogen (PL). These studies determined temporal and spatial alterations in PRL receptor (PRL-R) and expression of uterine milk proteins (UTMP), a mark er of endometrial secretory activity, in the ovine endometrium during the e strous cycle and pregnancy. Slot-blot hybridization analysis indicated that steady-state levels of endometrial PRL-R mRNA increased during pregnancy. In situ hybridization and immunohistochemical analyses indicated that PRL-R mRNA and protein were exclusively expressed in the endometrial glandular e pithelium (GE). No PRL-R mRNA expression was detected in luminal epithelium , stroma, myometrium, or conceptus trophectoderm. Reverse transcription-pol ymerase chain reaction analyses determined that the endometrial GE expresse d both long and short alternative splice forms of the ovine PRL-R gene. Slo t-blot hybridization analysis indicated that steady-state levels of interca runcular endometrial UTMP mRNA increased about 3-fold between Days 20 and 6 0, increased another 3-fold between Days 60 and 80, and then declined sligh tly to Day 120. In pregnant ewes, UTMP mRNA expression was restricted to th e endometrial CE in the stratum spongiosum (sGE), increased substantially b etween Days 15 and 17, and, between Days 17 to 50 of gestation, was markedl y higher in upper than lower sGE. After Day 50, hyperplasia of the sGE was accompanied by increased UTMP mRNA expression by all sGE. Collectively, res ults indicate that 1) endometrial sGE is a primary target for actions of la ctogenic hormones and 2) UTMP mRNA expression is correlated with PL product ion by the trophectoderm and state of sGE differentiation during pregnancy. It is proposed that activation of PRL-R signal transduction pathways by PR L and PL plays a major role in endometrial GE remodeling and differentiated function during pregnancy in support of conceptus growth and development.