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

Mol Cell Endocrinol. 2017 Jan 15;440:16-24. doi: 10.1016/j.mce.2016.11.006. Epub 2016 Nov 9.

Abstract

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.

Keywords: Dexamethasone; Epidermal growth factor; Glucocorticoid; Mammary epithelial cell; Prolactin; β-casein.

MeSH terms

  • Animals
  • Caseins / metabolism*
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Dexamethasone / pharmacology
  • Down-Regulation / drug effects
  • Epidermal Growth Factor / pharmacology*
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Female
  • Glucocorticoids / pharmacology*
  • Lactation / drug effects*
  • Mammary Glands, Animal / cytology*
  • Mice, Inbred ICR
  • Prolactin / pharmacology*
  • Qb-SNARE Proteins / metabolism
  • Qc-SNARE Proteins / metabolism
  • Secretory Pathway / drug effects*
  • Secretory Pathway / genetics
  • Sheep

Substances

  • Caseins
  • Glucocorticoids
  • Qb-SNARE Proteins
  • Qc-SNARE Proteins
  • Snap23 protein, mouse
  • Epidermal Growth Factor
  • Dexamethasone
  • Prolactin