LAUSR

5-hydroxytryptamine (5-HT) is an amine produced in both the mammary gland and the central nervous system. Tryptophan hydroxylase 1 (TPH1) catalyzes the conversion of 5-hydroxytryptophan (5-HTP) into L-tryptophan, which is then converted into 5-HT by monoamine-oxidase (MAO-A). In the mammary gland, 5-HT has been shown to have a variety of paracrine-autocrine actions, including suppressing lactation, controlling the destiny of mammary epithelial cells, and maintaining calcium homeostasis throughout the transition from pregnancy to lactation. To examine the effects of 5-HT on the composition of colostrum and milk, a total of 30 transition Guan Zhong dairy goats were intramuscularly injected with 5-HTP (1.0 mg/kg) every morning before feeding from 10 days before the projected parturition date to the day of parturition. The average number of days animals received injections was 8.2±3.2 days. 5-HTP treatment increased serum 5-HT concentration from day-5 to day -2 relative to parturition (P <0.05), and decreased the casein concentration of colostrum (P <0.05). In the in vitro experiment, mammary epithelial cells isolated from 3 individual goats' mammary gland were separately treated with 200 μM 5-HTP, 30 μM PCPA (the specific inhibitor of TPH1), or 200 μM 5-HTP + 50 μM SB269970(the selective antagonist of 5-HTR7). The results showed that 200 μM 5-HTP inhibited the expression of β-casein, down-regulated the activity of the JAK2/ STAT5a signaling pathway, and promoted the apoptosis of goat mammary epithelial cells (GMECs) (P <0.05). When GMECs were treated with 30 μM Four-chloro-DL-phenylalanine (PCPA), a specific inhibitor of 5-HT synthesis, the mRNA expression of STAT5a and the phosphorylated STAT5a protein level were up-regulated. The 50 μM SB269970 treatment rescued the effects of 5-HTP on GMECs (P <0.05). Taken together, the results indicated that 5-HTP exerted an inhibitory effect on β-casein synthesis and a pro-apoptotic effect in GMECs via HTR7 and the JAK2/STAT5a axis.