The Biological Activities of Vitamin D and Its Receptor in Relation to Calcium and Bone Homeostasis, Cancer, Immune and Cardiovascular Systems, Skin Biology, and Oral Health

Figure 2

Schematic representation of the functions of vitamin D in bone and calcium homeostasis. Low serum calcium triggers the production and secretion of parathyroid hormone (PTH) by the parathyroid glands, which in turn induces the synthesis of 1,25(OH)₂D in the kidney by CYP27B1. FGF 23 can inhibit renal tubular reabsorption of phosphate and CYP27B1 activity and can stimulate CYP24A1 [7, 8, 26, 27]. Vitamin D regulates calcium homeostasis by promotion of calcium absorption in the intestine, by reabsorption of calcium by the kidney, and by mobilization of calcium from the bone. 1,25(OH)₂D through a negative feedback loop regulates the synthesis of PTH and of CYP27B1 (a) [4–6, 10]. Lower 25(OH)D is associated with increased PTH levels and lower bone density. This is owing to PTH/Vitamin D-induced increase in bone turnover, which results in increased bone resorption. Persistent vitamin D deficiency may result in osteopenia and osteomalacia [5]. 1,25(OH)₂D promotes the production of CYP24A1, the enzyme that degrades 1,25(OH)₂D (b) [1, 5], and low calcium and low PTH levels inhibit the production of CYP24A1 (c) [4]. Thus levels of circulating 1,25(OH)₂D are regulated, in part, by CYP27B1-mediated production and by CYP24A1-mediated degradation [4].