Increased 25-hydroxyvitamin D3 1α-hydroxylase and reduced 25-hydroxyvitamin D3 24-hydroxylase expression in parathyroid tumors -: New prospects for treatment of hyperparathyroidism with vitamin D

Vitamin D analogues are in clinical use for prevention and treatment of secondary hyperparathyroidism (HPT) in chronic renal failure. Despite recent advances there is a need for vitamin D derivatives with maintained parathyroid hormone suppressive activity and less hypercalcemic and hyperphosphatemic toxicity. Here we show coincident increased expression of the vitamin D activating enzyme 25-hydroxyvitamin D-3 1alpha-hydroxylase (1alpha-hydroxylase) and reduced expression of the 1,25(OH)(2)D-3 catabolizing enzyme 25-hydroxyvitamin D-3 24-hydroxylase (24-hydroxylase) in the majority of investigated parathyroid adenomas and secondary hyperplastic glands. In addition, this relationship was found for the mitochondrial CYP27A enzyme (25-hydroxylase), a potential physiological vitamin D-3 25-hydroxylase. These findings should be considered in future development of vitamin D analogues for treatment of HPT.