J Anim Sci. 2017 Dec;95(12):5711-5719. doi: 10.2527/jas2017.1673.
The mammary gland regulates maternal metabolism during lactation. Numerous factors within the tissue send signals to shift nutrients to the mammary gland for milk synthesis. Serotonin is a monoamine that has been well documented to regulate several aspects of lactation among species. Maintenance of maternal calcium homeostasis during lactation is a highly evolved process that is elegantly regulated by the interaction of the mammary gland with the bone, gut, and kidney tissues. It is well documented that dietary calcium is insufficient to maintain maternal calcium concentrations during lactation, and mammals must rely on bone resorption to maintain normocalcemia. Our recent work focused on the ability of the mammary gland to function as an accessory parathyroid gland during lactation. It was demonstrated that serotonin acts to stimulate parathyroid hormone-related protein (PTHrP) in the mammary gland during lactation. The main role of mammary-derived PTHrP during mammalian lactation is to stimulate bone resorption to maintain maternal calcium homeostasis during lactation. In addition to regulating PTHrP, it was shown that serotonin appears to directly affect calcium transporters and pumps in the mammary gland. Our current working hypothesis regarding the control of calcium during lactation is as follows: serotonin directly stimulates PTHrP production in the mammary gland through interaction with the sonic hedgehog signaling pathway. Simultaneously, serotonin directly increases calcium movement into the mammary gland and, subsequently, milk. These 2 direct actions of serotonin combine to induce a transient maternal hypocalcemia required to further stimulate PTHrP production and calcium mobilization from bone. Through these 2 routes, serotonin is able to improve maternal calcium concentrations. Furthermore, we have shown that Holstein and Jersey cows appear to regulate calcium in different manners and also respond differently to serotonergic stimulation of the calcium pathway. Our data in rodents and cows indicate that serotonin and calcium are working through a unique feedback loop with PTHrP during lactation to regulate milk calcium and maternal calcium homeostasis.
乳腺在哺乳期调节母体代谢。组织内的许多因素向乳腺发送信号，将营养物质转移到乳腺以合成乳汁。血清素是一种单胺，已被充分证明可调节不同物种的泌乳的几个方面。在哺乳期维持母体钙稳态是一个高度进化的过程，乳腺与骨骼、肠道和肾脏组织的相互作用可以优雅地调节这一过程。有充分的文献记载表明，在哺乳期，膳食中的钙不足以维持母体钙浓度，哺乳动物必须依靠骨吸收来维持正常的血钙水平。我们最近的工作重点是研究乳腺在哺乳期作为辅助甲状旁腺的功能。研究表明，血清素在哺乳期作用于刺激乳腺中的甲状旁腺激素相关蛋白（PTHrP）。哺乳期间乳腺来源的 PTHrP 的主要作用是刺激骨吸收，以维持哺乳期母体钙稳态。除了调节 PTHrP 外，还表明血清素似乎直接影响乳腺中的钙转运体和泵。我们目前关于哺乳期钙控制的工作假设如下：血清素通过与 sonic hedgehog 信号通路相互作用，直接刺激乳腺中 PTHrP 的产生。同时，血清素直接增加钙向乳腺的运动，随后进入乳汁。血清素的这 2 个直接作用相结合，诱导暂时的母体低钙血症，以进一步刺激 PTHrP 的产生和骨钙动员。通过这 2 个途径，血清素能够提高母体钙浓度。此外，我们已经表明，荷斯坦牛和泽西牛似乎以不同的方式调节钙，并且对钙途径的血清素刺激反应也不同。我们在啮齿动物和奶牛中的数据表明，在哺乳期，血清素和钙通过与 PTHrP 的独特反馈环共同作用，调节乳汁钙和母体钙稳态。
