Distinct roles of prolactin, epidermal growth factor, and glucocorticoids in β-casein secretion pathway in lactating mammary epithelial cells

Beta-casein is a secretory protein contained in milk. Mammary epithelial cells (MECs) synthesize and secrete beta-casein during lactation. However, it remains unclear how the beta-casein secretion pathway is developed after parturition. In this study, we focused on prolactin (PRL), epidermal growth factor (EGF), and glucocorticoids, which increase in blood plasma and milk around parturition. MECs cultured with PRL, EGF and dexamethasone (DEX: glucocorticoid analog) developed the beta-casein secretion pathway. In the absence of PRL, MECs hardly expressed beta-casein. EGF enhanced the expression and secretion of beta-casein in the presence of PRL and DEX. DEX treatment rapidly increased secreted beta-casein concurrent with enhancing beta-casein expression. DEX also up-regulated the expression of SNARE proteins, such as SNAP-23, VAMP-8 and Syntaxin-12. Furthermore, PRL and DEX regulated the expression ratio of alpha(st-), beta- and kappa-casein. These results indicate that PRL, EGF and glucocorticoids have distinct roles in the establishment of beta-casein secretion pathway. (C) 2016 Elsevier Ireland Ltd. All rights reserved.