Peripheral serotonin regulates energy metabolism in several mammalian species, however, the potential contribution of serotonergic mechanisms as metabolic and endocrine regulators in growing dairy calves remain unexplored. Objectives were to characterize the role of serotonin in glucose and insulin metabolism in dairy calves with increased serotonin bioavailability. Milk replacer was supplemented with saline, 5-hydroxytryptophan (90 mg/d), or fluoxetine (40 mg/d) for 10-d (n = 8/treatment). Blood was collected daily during supplementation and on days 2, 7, and 14 during withdrawal. Calves were euthanized after 10-d supplementation or 14-d withdrawal periods to harvest liver and pancreas tissue. 5-hydroxytryptophan increased circulating insulin concentrations during the supplementation period, whereas both treatments increased circulating glucose concentration during the withdrawal period. The liver and pancreas of preweaned calves express serotonin factors (ie, TPH1, SERT, and cell surface receptors), indicating their ability to synthesize, uptake, and respond to serotonin. Supplementation of 5-hydroxytryptophan increased hepatic and pancreatic serotonin concentrations. After the withdrawal period, fluoxetine cleared from the pancreas but not liver tissue. Supplementation of 5-hydroxytryptophan upregulated hepatic mRNA expression of serotonin receptors (ie, 5-HTR1B, -1D, -2A, and -2B), and downregulated pancreatic 5-HTR1F mRNA and insulin-related proteins (ie, Akt and pAkt). Fluoxetine-supplemented calves had fewer pancreatic islets per microscopic field with reduced insulin intensity, whereas 5-hydroxytryptophan supplemented calves had increased islet number and area with greater insulin and serotonin and less glucagon intensities. After the 14-d withdrawal of 5-hydroxytryptophan, hepatic mRNA expression of glycolytic and gluconeogenic enzymes were simultaneously downregulated. Improving serotonin bioavailability could serve as a potent regulator of endocrine and metabolic processes in dairy calves.

外周血清素调节几种哺乳动物的能量代谢，然而，血清素能机制作为生长奶牛的代谢和内分泌调节剂的潜在贡献仍未得到探索。目的是表征血清素在具有增加的血清素生物利用度的奶牛犊的葡萄糖和胰岛素代谢中的作用。代乳品补充有生理盐水、5-羟色氨酸（90 毫克/天）或氟西汀（40 毫克/天），持续 10 天（n = 8/治疗）。在补充期间和停药期间的第 2、7 和 14 天每天收集血液。在 10 天补充或 14 天停药期后对小牛实施安乐死以收获肝脏和胰腺组织。5-羟色氨酸在补充期间增加循环胰岛素浓度，而两种治疗方法都增加了停药期间的循环葡萄糖浓度。断奶前犊牛的肝脏和胰腺表达血清素因子（即，TPH1、SERT和细胞表面受体），表明它们合成、吸收和响应血清素的能力。补充 5-羟色氨酸会增加肝脏和胰腺的血清素浓度。停药期后，氟西汀从胰腺中清除，但未从肝组织中清除。补充 5-羟色氨酸可上调血清素受体（即5-HTR1B、-1D、-2A和-2B）的肝脏 mRNA 表达，并下调胰腺5-HTR1FmRNA 和胰岛素相关蛋白（即 Akt 和 pAkt）。补充氟西汀的小牛每个显微镜视野中的胰岛较少，胰岛素强度降低，而补充 5-羟色氨酸的小牛的胰岛数量和面积增加，胰岛素和血清素增加，胰高血糖素强度降低。5-羟色氨酸停用 14 天后，肝糖酵解和糖异生酶的 mRNA 表达同时下调。提高血清素的生物利用度可以作为奶牛内分泌和代谢过程的有效调节剂。