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

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 beta-casein expression, a differentiation marker, produced in human mammary epithelial cells, and to determine whether 5-HT can attenuate beta-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 beta-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 beta-casein and phosphorylated STAT5 (pSTAT5) proteins in a concentration-dependent manner, with a slight increase of STAT5 protein. beta-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 beta-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 beta-Casein expression. In conclusion, we showed that exogenous 5-HT decreased beta-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.