Prolactin and glucocorticoid signaling induces lactation-specific tight junctions concurrent with β-casein expression in mammary epithelial cells

Biochim Biophys Acta. 2016 Aug;1863(8):2006-16. doi: 10.1016/j.bbamcr.2016.04.023. Epub 2016 Apr 26.


Alveolar mammary epithelial cells (MECs) in mammary glands are highly specialized cells that produce milk for suckling infants. Alveolar MECs also form less permeable tight junctions (TJs) to prevent the leakage of milk components after parturition. In the formation process of less permeable TJs, MECs show a selective downregulation of Cldn4 and a localization change of Cldn3. To investigate what induces less permeable TJs through these compositional changes in Cldns, we focused on two lactogenesis-related hormones: prolactin (Prl) and glucocorticoids. Prl caused a downregulation of Cldn3 and Cldn4 with the formation of leaky TJs in MECs in vitro. Prl-treated MECs also showed low β-casein expression with the activation of STAT5 signaling. By contrast, dexamethasone (Dex), a glucocorticoid analogue, upregulated Cldn3 and Cldn4, concurrent with the formation of less permeable TJs and the activation of glucocorticoid signaling without the expression of β-casein. Cotreatment with Prl and Dex induced the selective downregulation of Cldn4 and the concentration of Cldn3 in the region of TJs concurrent with less permeable TJ formation and high β-casein expression. The inhibition of Prl secretion by bromocriptine in lactating mice induced the upregulation of Cldn3 and Cldn4 concurrent with the downregulation of milk production. These results indicate that the coactivation of Prl and glucocorticoid signaling induces lactation-specific less permeable TJs concurrent with lactogenesis.

Keywords: Epithelial cell; Glucocorticoid; Mammary gland; Prolactin; Tight junction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caseins / biosynthesis*
  • Caseins / genetics
  • Cell Membrane Permeability / drug effects
  • Cells, Cultured
  • Claudin-3 / biosynthesis*
  • Claudin-3 / genetics
  • Claudin-4 / biosynthesis*
  • Claudin-4 / genetics
  • Dexamethasone / pharmacology*
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Female
  • Gene Expression Regulation / drug effects
  • Lactation / drug effects*
  • Lactation / physiology
  • Mammary Glands, Animal / cytology*
  • Mice
  • Mice, Inbred ICR
  • Pregnancy
  • Prolactin / pharmacology*
  • STAT5 Transcription Factor / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Tight Junctions / drug effects*
  • Tight Junctions / physiology


  • Caseins
  • Claudin-3
  • Claudin-4
  • Cldn3 protein, mouse
  • Cldn4 protein, mouse
  • STAT5 Transcription Factor
  • Dexamethasone
  • Prolactin