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

•Prolactin is indispensable for initiation of β-casein synthesis.•Epidermal growth factor up-regulate β-casein expression.•Glucocorticoids activate β-casein secretion with enhancing β-casein expression.•Prolactin and glucocorticoids change the expression ratio of casein subtypes.

Beta-casein is a secretory protein contained in milk. Mammary epithelial cells (MECs) synthesize and secrete β-casein during lactation. However, it remains unclear how the β-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 β-casein secretion pathway. In the absence of PRL, MECs hardly expressed β-casein. EGF enhanced the expression and secretion of β-casein in the presence of PRL and DEX. DEX treatment rapidly increased secreted β-casein concurrent with enhancing β-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 αs1-, β- and κ-casein. These results indicate that PRL, EGF and glucocorticoids have distinct roles in the establishment of β-casein secretion pathway.