Modulation of α2β1 integrin changes during mammary gland development by β-oestradiol

AbstractIn order to study the role of cell–matrix interactions in mammary gland function, temporal changes in α2β1 integrin, the major receptor for collagen and the influence of β-oestradiol on its level and distribution in rat mammary gland at different stages of development were studied. The level of α2β1 integrin determined by ELISA, was found to be high during different days of pregnancy, while in the lactating stage, it was significantly reduced. By immunocytochemical analysis, α2β1 integrin was found to be localized towards the luminal side of acinar cells, both in the virgin and midpregnant stage, while it was not detected in the lactating stage. The possible role of hormones in modulating the level of integrin was examined in both in vitro and in vivo experiments using β-oestradiol. Supplementing β-oestradiol to isolated mammary epithelial cells from both virgin and lactating glands caused a concentration dependent increase in the incorporation of [35S]methionine into α2β1 integrin associated with the cells. Administration of β-oestradiol to virgin and lactating glands caused about 1.4–4-fold increase in the level of α2 integrin, indicating that upregulation of integrin during pregnancy may be due to oestrogen and as the oestrogen level falls during lactating phase, downregulation of α2β1 integrin occurs. Treatment with β-oestradiol also resulted in the appearance of α2β1 integrin in the acinar region of the lactating tissue, while in the untreated controls no staining for integrin was seen. These results indicate that oestrogen, apart from directly affecting the cellular activity, can influence mammary tissue function by affecting cell–ECM interactions through the modulation of integrin receptors for matrix proteins