Serotonin suppresses β-casein expression via inhibition of the signal transducer and activator of transcription 5 (STAT5) protein phosphorylation in human mammary epithelial cells MCF-12A

Biol Pharm Bull. 2014;37(8):1336-40. doi: 10.1248/bpb.b14-00273.


Serotonin (5-hydroxytryptamine; 5-HT) has an important physiological role in controlling lactation, namely, milk volume homeostasis, within mammary glands. The objectives of this study were to evaluate whether exogenous 5-HT can suppress β-casein expression, a differentiation marker, produced in human mammary epithelial cells, and to determine whether 5-HT can attenuate β-casein signaling via the prolactin (PRL) receptor (PRLr) and Janus kinase 2/signal transducer and activator of transcription 5 (STAT5) pathway. PRL treatment increased the mRNA level of β-casein in the MCF-12A human mammary epithelial cell line, and the highest level occurred at days 7 and 14 of culture. In contrast, PRLr expression was not affected significantly by PRL treatment. PRL treatment in MCF-12A cells increased levels of β-casein and phosphorylated STAT5 (pSTAT5) proteins in a concentration-dependent manner, with a slight increase of STAT5 protein. β-Casein expression was inhibited by 0.1 mM 5-HT in a time-dependent manner. Additionally, treatment with 0.1 mM 5-HT for 72 h decreased protein levels of β-casein and pSTAT5, with a slight decrease in STAT5 levels. These results suggest that exogenous 5-HT can inhibit STAT5 phosphorylation, resulting in a decrease in β-Casein expression. In conclusion, we showed that exogenous 5-HT decreased β-casein expression in MCF-12A human mammary epithelial cells, and that 5-HT was responsible for inhibiting phosphorylation of STAT5, resulting in a decline in lactational function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast
  • Caseins / genetics*
  • Caseins / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Humans
  • Janus Kinase 2 / metabolism
  • Phosphorylation
  • Prolactin / pharmacology
  • RNA, Messenger / metabolism
  • Receptors, Prolactin / genetics
  • STAT5 Transcription Factor / antagonists & inhibitors*
  • STAT5 Transcription Factor / metabolism
  • Serotonin / pharmacology*


  • Caseins
  • RNA, Messenger
  • Receptors, Prolactin
  • STAT5 Transcription Factor
  • Serotonin
  • Prolactin
  • JAK2 protein, human
  • Janus Kinase 2