| Extracellular calcium (Ca2+) concentrations are tightly regulated by complex homeostatic mechanisms, including parathyroid hormone (PTH), calcitonin, and 1,25-dihydroxyvitamin D (calcitriol). PTH is secreted by chief cells of the parathyroid gland, and is considered the most important calcium-regulating hormone. In vitro studies in parathyroid chief cells from different species have improved our understanding on the physiology and pathophysiology of the parathyroid gland. However, there is limited information on parathyroid gland function in horses. Horses have unique features with regard to calcium metabolism, including high serum Ca 2+ concentrations, high urinary fractional clearance of calcium, low serum concentrations of vitamin D (1,25-dihydroxyvitamin D, 25-hydroxyvitamin D), and an increased Ca2+ set-point (Ca2+ concentration at which PTH secretion is 50% maximal). Several pathological conditions in horses are associated with abnormal calcium homeostasis. We have determined that in the horse (as occurs in other species) the Ca2+/PTH relationship is sigmoidal, and the Ca2+ set-point is higher than in other domestic animals and man, which may, in part, explain the high serum calcium concentrations of the horse. Hypocalcemia occurs frequently in humans with sepsis. We found that sepsis (enterocolitis) in horses was associated with hypocalcemia, and that some horses did not have the expected increase in serum PTH concentrations for the degree of hypocalcemia, suggesting impaired parathyroid gland function. When equine parathyroid cells were studied in vitro for 30 days, we determined that, over time in culture there was a decrease in PTH secretion, and in PTH and calcium-sensing receptor (CaR) mRNA expression. Furthermore, equine parathyroid cells exposed to an inflammatory mediator, interleukin-1β (IL-1β), had decreased PTH secretion and PTH mRNA expression, and increased CaR mRNA expression compared to controls, indicating that IL-1β may play a role in regulating chief cell function in the horse. We cloned, sequenced, and determined the tissue expression of calcitonin, calcitonin gene-related peptide (CGRP)-I, and CGRP-I in the horse. Information from these genes will be valuable to further study of the role of the calcitonin gene family in calcium regulation in healthy and sick horses. Calcium homeostasis is a complex process that involves many regulatory factors. Disturbances of calcium regulation are frequent in human and veterinary medicine. With our studies we have provided additional information to understand calcium regulation in horses. |
