MODULATION OF HEPATOCYTE GROWTH-FACTOR AND C-MET IN THE RAT MAMMARY-GLAND DURING PREGNANCY, LACTATION, AND INVOLUTION

Epithelial tubulogenesis is responsible for the exquisitely intricate organization of functional units of parenchymal organs. We have previo usly demonstrated that hepatocyte growth factor (HGF-also known as sca tter factor) is a stroma-derived epithelial morphogen, which induces t ubulogenesis by kidney-derived epithelial cells in vitro. The mammary gland provides a particularly attractive model for the study of epithe lial morphogenesis, since its development in postnatal life involves e longation and branching of epithelial tubules. The aim of the present studies was to assess the expression and modulation of HGF and its rec eptor c-Met in the rat mammary gland during pregnancy, lactation, and involution. By ribonuclease protection assay, we demonstrate that leve ls of both HGF and c-met transcripts are progressively reduced during pregnancy, are virtually undetectable during lactation, and increase d uring the phase of involution to prepregnancy levels. The reduction in HGF and c-met expression corresponds to periods in which functions ot her than tubulogenesis predominate in the mammary gland, namely alveol ogenesis (mid to late pregnancy) and milk protein synthesis (lactation ). Using a murine mammary gland-derived epithelial cell line, we demon strate that levels of c-met mRNA are significantly reduced by exogenou sly added prolactin, providing a possible explanation for the reductio n in c-met in the rat mammary gland during lactation. The potential si gnificance of down-regulation of HGF/c-met during lactation is discuss ed. (C) 1995 Academic Press, Inc.