Serotonin Suppresses β-Casein Expression <i>via</i> Inhibition of the Signal Transducer and Activator of Transcription 5 (STAT5) Protein Phosphorylation in Human Mammary Epithelial Cells MCF-12A

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  • Chiba Takeshi
    Department of Clinical Pharmaceutics and Pharmacy Practice, School of Pharmacy, Iwate Medical University
  • Kimura Soichiro
    Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Josai University
  • Takahashi Katsuo
    Department of Clinical Pharmaceutics and Pharmacy Practice, School of Pharmacy, Iwate Medical University
  • Morimoto Yasunori
    Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Josai University
  • Sanbe Atsushi
    Department of Pharmacotherapeutics, School of Pharmacy, Iwate Medical University
  • Ueda Hideo
    Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Josai University
  • Kudo Kenzo
    Department of Clinical Pharmaceutics and Pharmacy Practice, School of Pharmacy, Iwate Medical University

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  • 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

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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.

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