Recent studies show that progestin and relaxin synergistically induce the production of prolactin (PRL) and other cellular proteins in human endometrial stromal cells. The concerted effects of progestin and relaxin on the induction of prolactin are closely associated with the growth and decidualization of the endometrial stromal cells at the time of conception and during pregnancy. The long term goal of this project is to investigate the role of individual hormones on the induction of PRL at different stages of the development of endometrial stromal cells. The project proposes to investigate the mechanism of action of progestin and relaxin on the various levels of PRL gene expression and the development of human endometrial stromal cells in a long-term culture system. (1) The rate of PRL synthesis, steady-state levels of PRLmRNA, the rate of degradation of PRLmRNA, and the rate of transcription of PRLmRNA, will be investigated at the initial phase and during the continuing PRL production period. (2) The development of endometrial stromal cells under the influence of progestin and relaxin in vitro will be studied by comparing the induction pattern of PRL in the stromal cells to that in the decidua, a fully differentiated endometrium; and by investigating DNA synthesis, total DNA and protein contents. (3) The second messenger(s) of relaxin and the transmembrane signal pathways which transmit the signal of relaxin to activate the PRL gene expression will be investigated in progestin-primed endometrial stromal cells and in decidual cells. This project provides a system to study the PRL gene expression during the differentiation of the endometrium, a biological system uniquely different from the pituitary system. This proposal will demonstrate the transformation of a hormone target tissue (the endometrium) into an autocrine system (the decidua). Understanding the role of relaxin and endogenous hormone on decidualization will improve the successful rate of implantation. It will also offer new pharmacological avenues to fertility regulation and the development of new contraceptive agents, the prevention and treatment of reproductive dysfunction and neoplastic transformation of the endometrium.
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