Increased 25-Hydroxyvitamin D3 1{alpha}-Hydroxylase and Reduced 25-Hydroxyvitamin D3 24-Hydroxylase Expression in Parathyroid Tumors: New Prospects for Treatment of Hyperparathyroidism with Vitamin D

Pamela Correa, Ulrika Segersten, Per Hellman, Göran Åkerström and Gunnar Westin

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{alpha}-hydroxylase (1{alpha}-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.