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Hepatocyte Growth Factor System in the Mouse Uterus: Variation Across the Estrous Cycle and Regulation by 17-Beta-Estradiol and Progesterone1

Hepatocyte growth factor (HGF) and its receptor MET have been implicated in uterine development, pregnancy, and endometrial disorders, such as endometriosis and carcinoma. In vitro studies have shown that HGF acts as a mitogen, motogen, and morphogen on endometrial epithelial cells. However, the expression and regulation of HGF and MET in the uteri of different species remain obscure. The present study aimed to investigate the changes of HGF, MET, and HGF activator (HGFA) expression in the uterine endometrium during the estrous cycle in mice and to explore estrogen and progesterone regulation of their expression. MKI67 immunostaining was conducted to examine the association between HGF/MET expression and endometrial cell proliferation. Endometrial epithelial and stromal cells both expressed HGF, HGFA, and MET, but the cell type-specific patterns changed during the cycle. Estrogen and progesterone differentially regulated HGF, MET, and HGFA expression. Progesterone up-regulated their expression in the stroma and down-regulated their expression in the luminal epithelium, whereas 17-beta-estradiol down-regulated their expression in the glandular epithelium. The pattern of HGF/MET overall correlated with that of MKI67. In conclusion, HGF, HGFA, and MET expression in mouse uterus changes during the estrous cycle in a stage-, cell type-, and compartment-specific manner under the influence of estrogen and progesterone. HGF likely plays a role in cyclic endometrial remodeling, such as cell proliferation via autocrine/paracrine mechanisms in mouse uterus.