Vitamin D metabolism and function
Metabolism of vitamin D is intricately linked to the endocrine control of calcium and phosphorus homeostasis and involvE!s the parathyroid and thyroid glands. The primary site of control of vitamin D metabolism appears to be the renal synthesis of 1,25-(OH)2D3, which responds to changes in the body's need for calcium and phosphorus. Hypocalcemia stimulates the parathyroid gland to release PTH, which, in turn, increases the activity ofrena11-hydroxylase (25-hydroxycholecalciferol-1-hydrm.'ylase) and, consequen tly, the level of circula ting 1,25-( OH) 2D3' 32,36 However, the most immediate effect is the mobilization of calcium from the bone by PTH with the existing 1,25-(OH)2D3' Both also cause increased reabsorption of calcium by the kidneys, but independently and at different sites. These two mechanisms are responsible for restoring the plasma calcium and plasma phosphorus levels. The specific effects of PTH on phosphorus are discussed in Chapter 6. The elevation of 1,25-(OH)2D3 eventually increases the intestinal absorption of calcium and phosphorus, but this action is more important in replenishing the bone minerals to maintain calcium and
phosphorus balance than in the short-term control of lasma levels.
When the plasma calcium reaches a normal level, the production of PTH decreases and results in the suppression of 1-hydroxylase in the kidney. Suppression of this enzyme by its product 1,25-(OH)2D3 has been observed, but as with some other factors, it may not have a direct ect on the enzyme as much as a secondary one due to :-educed PTH. 36 In hypercalcemia, calci tonin is released by the thyroid gland, blocking further mobilization of bone ::ninerals. High plasma calcium concentration turns off the production of PTH and, secondarily, 1,25-(OH)2D3' ''-ereby reducing calcium flow from all three sites.
Hypophospha temia also increases the level of :.25-(OH)2D3 as part of the changes initiated to restore plasma phosphorus level, but the magnitude of the response is much smaller than that produced by hypocalcemia.
There is also evidence tha t other hormones playa role of the regulation of vitamin D metabolism. Prolactin, growth hormone and insulin have been reported to simulate formation of 1,25-(OH)2D3. Whether these hormones affect vitamin D metabolism directly or indirectly remains uncertain.
Concentration of 1,25-(OH)2D3 in the plasma is much lower than that of 25-0H-D3 and its life is only 5 to 8 hours compared with 15 to 30 days :or 25-0H-D3. Although the synthesis of 25-0H-D3 in;:reases, following administration of vitamin D3, the inceased supply of substrate does not affect the rate of the renal production of 1,25-(OH)2D3. Consequently, the hepatic 25-hydroxylase does not appear to be part of the regulatory system that controls the level of active vitamin D in the body. The physiological significance and control of the 24-hydroxylation of 25-0H-D3 and 1,25-(OH)2D3 remain to be clarified.
