Serotonin regulates maternal calcium homeostasis during the perinatal period of sheep.

The goal of this experiment was to demonstrate the ability of an infusion of serotonin (5-HT; 5-hydroxytryptamine) precursors to increase 5-HT production during the transition from pregnancy to lactation and its effects on gene expression related to calcium (Ca) transporters in the mammary gland and bone resorption markers in the femur. Thirty pregnant Bamei mutton sheep were randomly assigned to 3 experimental groups. All groups received a daily intravenous infusion of saline (control group; n = 10), saline containing 0.178 mg of L-tryptophan/kg body weight (BW) (TRP group, n = 10) or 0.178 mg of 5-hydroxytryptophan/kg BW (5-HTP group, n = 10), beginning on day 7 of prepartum and continuing until delivery. Serum (pre- and postpartum), milk (postpartum), and femur and mammary gland tissue (day 9) were collected. Sheep infused with 5-HTP had a larger total serum Ca concentration on days 3, 6, 15, and 30 of lactation and total milk Ca concentration on days 3, 6, 12, and 15 of lactation compared with that of the control group. Sheep infused with 5-HTP and TRP increased blood and milk concentrations of 5-HT on days 3, 6, 9, and 30 of lactation and parathyroid hormone-related protein (PTHrP) on day 3 of prepartum and on days 3, 6, and 15 of lactation (P < 0.05). In addition, compared to that of the control group, the TRP or 5-HTP infusion upregulated PTHrP, a sodium/calcium exchanger, plasma membrane Ca2+ ATPase 2, secretory pathway Ca2+ ATPase 1, and calcium sensing receptor mRNA expression in mammary gland and receptor-activated nuclear factor kappa-B ligand mRNA expression in the femur, but had no effect on receptor-activated nuclear factor kappa-B and osteoprotegerin mRNA expression in the femur (P < 0.05). This suggests that 5-HT and PTHrP may be involved in regulating maternal Ca homeostasis during the transition from pregnancy to lactation in the sheep.