Regulation of Parathyroid Hormone Gene Expression and Secretion by Vitamin D

Abstract

The discovery of the action of vitamin D on the parathyroids, with its therapeutic implications, is one of the success stories of clinical medicine. Vitamin D’s classical sites of action were well known to be on the intestine (to increase calcium absorption) and on bone (to promote normal mineralization). With the discovery in 1970 by Fraser (1) that the kidney produced a more polar hydroxylated metabolite and the subsequent identification of this metabolite by Fraser and De Luca (2) as 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], it then became possible to study the biochemical and physiologic effects of vitamin D in greater depth. In the 1970s 1,25(OH)2D3 was shown to be effective for the treatment of renal bone disease, in particular the osteomalacic component, and in addition the features of secondary hyperparathyroidism. It was thought that the effect on the secondary hyperparathyroidism of 1,25(OH)2D3 was due to the increased intestinal absorption of calcium and the increased levels of serum calcium, leading to a decrease in parathyroid hormone (PTH) secretion. This is certainly correct, but it is only part of the story. It was later shown by a number of in vitro and in vivo studies that 1,25(OH)2D3 also has a direct action on the parathyroid. The use of 1,25(OH)2D3 is one of the cornerstones of secondary hyperparathyoidism management in all patients with chronic renal failure. This effect is discussed here.