Serotonin found to be an important factor in calcium homeostasis in dairy cows

New review in the Journal of Dairy Science® explores the role of serotonin during the peripartum period and its relationship with calcium

Philadelphia, November 16, 2021 – Maternal physiology of dairy cows shifts at the onset of lactation to adapt to the immense nutrient demands by the mammary gland, resulting in altered tissue metabolism. Research over the last decade has focused on understanding the shift in calcium metabolism, with an emphasis on the relationship of serotonin with calcium during the transition period and lactation. In a new review in the December issue of the Journal of Dairy Science® researchers examine the current knowledge on calcium metabolism, mammary calcium transport, serotonin metabolism, and the serotonin-calcium axis.

This review by scientists from the Department of Animal and Dairy Sciences, University of Wisconsin, Madison (USA), focuses on dairy cows during the period just before, during, and after giving birth. “Due to the rapid and robust demand for calcium at the onset of lactation by the mammary gland, a dynamic change in calcium metabolism ensues as the mammary gland’s demand for calcium in the blood and extracellular pools outpaces the rate at which pools can be maintained,” said first author Meghan K. Connelly, PhD student.

Without accommodating for this shift in calcium metabolism, disruptions in calcium balance can lead to an increased risk of displaced abomasum, ketosis, mastitis, and metritis. Research has found that as much as 50% of cows who have previously given birth experience subclinical hypocalcemia, with older cows experiencing greater calcium balance disruptions than cows who have not previously given birth.

Caption: Working model for direct and indirect mechanisms of mammary serotonin (5HT)-stimulated improvements of Ca metabolism. Increased 5HT concentrations induce changes in key Ca transporters (ORAI1 and PMCA2). Increased expression of ORAI1 and PMCA2 will result in Ca excreted into milk, resulting in transient hypocalcemia (A). The resulting declines in blood Ca concentrations inactivate the Ca sensing receptor (CaSR), stimulating synthesis and secretion of parathyroid hormone-related protein (PTHrP) by the mammary gland, indirectly modulating Ca metabolism (B). Serotonin may directly stimulate mammary-derived PTHrP (C). Upon release into circulation, PTHrP may then travel to bone, bind, and act to liberate bone Ca stores to recover blood Ca concentrations (D) (Credit: Journal of Dairy Science).

Blood calcium levels are tightly regulated through an integrated homeostatic process that is controlled by hormones, vitamin D, and proteins in a negative-feedback loop. The synthesis and secretion of these hormones, including parathyroid hormone-related peptide (PTHrP), is prompted by low blood calcium concentrations. More recently, PTHrP has been found to correlate with serotonin during lactation.

Recent data have shown that lactation results in a substantial increase in serotonin concentrations in the blood. “Recently, an interesting relationship between serotonin and calcium has been demonstrated during lactation, with significant changes in both calcium and serotonin physiology occurring at the onset of lactation and being mammary driven,” said Connelly.

Mammary serotonin drives mammary production of hormones and peptides that ultimately modulate mammary calcium transport. Additionally, prepartum infusion of 5-HTP (the immediate precursor to serotonin) increases serotonin levels in the adult dairy cow and improves calcium metabolism postpartum. This increase in serotonin is thought to cause a transient hypocalcemia as calcium is directed out of blood and into milk. The resulting decrease in calcium concentration in blood allows the bone to release calcium into peripheral pools to support mammary calcium demand, driving calcium metabolism.

The review concludes with strategies to mitigate hypocalcemia, including feeding a negative dietary cation-anion difference diet or a calcium binder for prevention, or oral, intravenous, and subcutaneous calcium therapies postpartum for treatment. Connelly and colleagues note that although the exact mechanisms of serotonin’s ability to improve calcium metabolism remain unclear, further consideration of serotonin as a hormone in calcium metabolism is warranted.

Notes for editors
The article is “Graduate Student Literature Review: Serotonin and calcium metabolism: A story unfolding,” by Meghan K. Connelly, Adrienne A. Cheng, and Laura L. Hernandez ( It appears online in advance of the Journal of Dairy Science, volume 104, issue 12 (December 2021), published by Fass Inc. and Elsevier.

This review is openly available at

Full text of the article is also available to credentialed journalists upon request. Contact Eileen Leahy at +1 732 238 3628 or to obtain copies. Journalists wishing to interview the authors should contact the corresponding author, Meghan K. Connelly, University of Wisconsin, Madison, at

About the Journal of Dairy Science
The Journal of Dairy Science® (JDS), an official journal of the American Dairy Science Association®, is co-published by Elsevier and Fass Inc. for the American Dairy Science Association. It is the leading general dairy research journal in the world. JDS readers represent education, industry, and government agencies in more than 70 countries, with interests in biochemistry, breeding, economics, engineering, environment, food science, genetics, microbiology, nutrition, pathology, physiology, processing, public health, quality assurance, and sanitation. JDS has a 2020 Journal Impact Factor of 4.034 and five-year Journal Impact Factor of 4.354 according to Journal Citation Reports (Source: Clarivate 2021).

About the American Dairy Science Association (ADSA)
The American Dairy Science Association (ADSA) is an international organization of educators, scientists, and industry representatives who are committed to advancing the dairy industry and keenly aware of the vital role the dairy sciences play in fulfilling the economic, nutritive, and health requirements of the world's population. It provides leadership in scientific and technical support to sustain and grow the global dairy industry through generation, dissemination, and exchange of information and services. Together, ADSA members have discovered new methods and technologies that have revolutionized the dairy industry.

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Since 1998, Fass has provided shared management services to not-for-profit scientific organizations. With combined membership rosters of more than 10,000 professionals in animal agriculture and other sciences, Fass offers clients services in accounting, membership management, convention and meeting planning, information technology, and scientific publication support. The Fass publications department provides journal management, peer-review support, copyediting, and composition for this journal; the staff includes five BELS-certified ( technical editors and experienced composition staff.

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