Leptin inhibits hepatocyte growth factor-induced ductal morphogenesis of bovine mammary epithelial cells

We examined the effect of stroma-derived factors, hepatocyte growth fac- tor(HGF)and leptin, on morphological differentiation of bovine mammary epi- thelial cells(BMEC)in collagen gel three-dimensional culture in vitro. BMEC treated with HGF, but not leptin, formed duct-like organoids. The formation of organoids by HGF was enhanced by treatment with a mixture of insulin, corti- sol and prolactin, while BMEC treated with the mixture alone did not produce the organoid. In contrast, the formation of organoids by HGF was dose- dependently inhibited by simultaneous addition of leptin, regardless of the presence or absence of the hormone mixture. These results suggest that stroma-derived factors intricately regulate mammary epithelial morphogene- sis.