Regulation of vitamin D metabolism
The main function of vitamin D is in the control of calcium homeostasis and, in turn, vitamin D metabolism in the kidney is regulated, at the level of 1- or 24-hydroxylation, by factors that respond to plasma concentrations of calcium and phosphate. In tissues other than the kidney that hydroxylate calcidiol to calcitriol, the enzyme is not regulated in response to plasma calcium.
● Calcitriol acts to reduce its own synthesis and increase formation of 24-hydroxycalcidiol, by regu-lating the expression of the genes for the two hydroxylases.
● Parathyroid hormone is secreted in response to a fall in plasma calcium. In the kidney it acts to increase the activity of calcidiol 1-hydroxylase and decrease that of 24-hydroxylase. In turn, both cal-citriol and high concentrations of calcium repress the synthesis of parathyroid hormone; calcium also inhibits the secretion of the hormone from the parathyroid gland.
● Calcium exerts its main effect on the synthesis and secretion of parathyroid hormone. However, calcium ions also have a direct effect on the kidney, reducing the activity of calcidiol 1-hydroxylase.
● Phosphate also affects calcidiol metabolism; throughout the day there is an inverse fluctuation of plasma phosphate and calcitriol, and feeding people on a low-phosphate diet results in increased circulating concentrations of calcitriol.