Department of Surgical Sciences, Endocrine Unit, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
Address correspondence to: Gunnar Westin, M.D., Department of Surgical Sciences, Endocrine Unit, Uppsala University, Klinisk forskningsavdelning 2, ingang 70, plan 3, lab 9, SE-751 85 Uppsala, Sweden.
Abstract
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 D3 1-hydroxylase (1
-hydroxylase)
and reduced expression of the 1,25(OH)2D3
catabolizing enzyme 25-hydroxyvitamin D3
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 D3
25-hydroxylase. These findings should be considered in future
development of vitamin D analogues for treatment of HPT.