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Serotonin: A new player in hypocalcemia
Dairy cows are challenged to maintain calcium homeostasis during the early post-partum due to increased demand by the mammary gland for calcium secretion into milk. The mammary gland coordinates the cow’s metabolism during lactation to ensure appropriate milk formation. Calcium is the major mineral constituent of milk. All mammals must mobilize bone tissue to maintain appropriate circulating calcium concentrations during lactation and support milk formation. Due to the high level of milk production seen in dairy cattle, approximately 47% of multiparous and 25% of primiparous cows have circulating calcium levels in the range of subclinical hypocalcemia (1.4-2.1 mM), approximately 5% are in the clinical range (<1.4 mM). Current therapies for the treatment and prevention and treatment of hypocalcemia include manipulation of the dietary cation-anion difference, oral calcium supplementation and intravenous calcium as a last resort. However, while these current strategies have been helpful for the prevention of clinical hypocalcemia, subclinical hypocalcemia is still prevalent. Recently, we have demonstrated the regulation of calcium homeostasis during early lactation by the monoamine, serotonin (5-HT). Serotonin acts to increase mammary gland production of parathyroid hormone related-protein, the hormone responsible for the mobilization of calcium from bone during lactation. Concentrations of 5-HT concentrations are dynamic over the course of a lactation cycle in multiparous dairy cows and greatly fluctuate around calving in multiparous cows follow a pattern similar to that of total calcium concentrations. 5-HT concentrations are positively correlated with total calcium and PTHrP on d 1 of lactation and negatively correlated with incidence of subclinical hypocalcemia in multiparous dairy cows. Furthermore, circulating 5-HT levels are positively correlated with total calcium concentrations during the first 10 days of lactation. Using a rat model we fed a precursor to 5-HT, 5-hyrdoxytryptophan (5-HTP) to rats during the transition from pregnancy to lactation in order to determine the feasibility of using 5-HT as a preventative strategy for hypocalcemia. Our results showed improved circulating calcium levels and increased calcium secretion into milk. In a preliminary acute 5-HTP dosing experiment in late lactation multiparous dairy cows, we observed that administration of 5-HTP improves calcium and glucose homeostasis. In conclusion, 5-HT is an important modulator of calcium and glucose homeostasis, and is of particular importance around the time of parturition.
Keywords: Serotonin, transition cow, hypocalcemia