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In the current study, we explored the relationship between melatonin and lactose synthesis in in vivo and in vitro conditions. We found that long-term melatonin feeding to the dairy cows significantly reduced the milk lactose content in a dose dependent manner. This lactose reduction was not associated with a negative energy balance, since melatonin treatment did not alter the fat, glucose, or protein metabolisms of the cows. To identify the potential molecular mechanisms, the cow’s mammary epithelial cells were cultured for gene expression analysis. The results showed that the effect of melatonin on lactose reduction was mediated by its receptor MT1. MT1 activation downregulated the mRNA expression of the prolactin receptor gene (PRLR), which then suppressed the gene expression of SLC35B1. SLC35B1 is a galactose transporter and is responsible for the transportation of galactose to Golgi apparatus for lactose synthesis. Its suppression reduced the lactose synthesis and the milk lactose content. The discovery of this signal transduction pathway of melatonin on lactose synthesis provides a novel aspect of melatonin’s effect on carbohydrate metabolism in cows and maybe also in other mammals, including humans.

Cow mastitis is a major problem frequently encountered by dairy farmers and it is manifested by the high number of somatic cells and the low quality of the milk. The conventional treatment for mastitis is use of antibiotics. In the current study, a new approach is applied to target this disorder: rumen bypass melatonin feeding (RBMF). The RBMF significantly reduced milk somatic cell count and improved milk nutritional values with the elevated protein, fat and dry matter levels. This approach also suppresses the stress and proinflammatory responses of the cows indicated by the reduced serum cortisol, TNF-α and IL-6 and increased IL-10 levels. Importantly, the beneficial effects of RBMF have lasted for several days after termination of the treatment. The effects of melatonin on the mastitis are probably attributed to the antioxidant and anti-inflammatory activities of melatonin. Considering the none or low toxicity of melatonin to organisms and the no invasive nature of this approach, we recommend that RBMF could be used in large scale in the dairy farming to target the cow mastitis.