Lactose on the basolateral side of mammary epithelial cells inhibits milk production concomitantly with signal transducer and activator of transcription 5 inactivation.

Mammary epithelial cells (MECs) are the only cells capable of synthesizing lactose. During lactation, alveolar MECs secrete lactose through the apical membrane into the alveolar lumen, whereas alveolar tight junctions (TJs) block the leakage of lactose into the basolateral sides of the MECs. However, lactose leaks from the alveolar lumen into the blood plasma in the mastitis and after weaning. This exposes the basolateral membrane of MECs to lactose. The relationship between lactose in blood plasma and milk production has been suggested. The present study determined whether lactose exposure on the basolateral membrane of mouse MECs adversely affects milk production in vitro. Restricted exposure to lactose on the basolateral side of the MECs was performed using a culture model, in which MECs on the cell culture insert exhibit milk production and less-permeable TJs. The results indicated that lactose exposure on the basolateral side inhibited casein and lipid production in the MECs. Interestingly, lactose exposure on the apical side did not show detectable effects on milk production in the MECs. Basolateral lactose exposure also caused the inactivation of STAT5, a primary transcriptional factor for milk production. Furthermore, p38 and JNK were activated by basolateral lactose exposure. The activation of p38 and JNK following anisomycin treatment reduced phosphorylated STAT5, and inhibitors of p38 blocked the reduction of phosphorylated STAT5 by basolateral lactose exposure. These findings suggest that lactose functions as a partial inhibitor for milk production but only when it directly makes contact with the basolateral membrane of MECs.