Increased 25-hydroxyvitamin D3 1alpha-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 expressions of the 1,25(OH)(2)D(3) catabolizing enzyme 25-hydroxyvitamin D(3) 1alpha-hydroxylase (1alpha-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.
Correa
Pamela
P
Department of Surgical Sciences, Endocrine Unit, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
Segersten
Ulrika
U
Hellman
Per
P
Akerstrom
Goran
G
Westin
Gunnar
G
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism*; D000236:Adenoma / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism; D006801:Humans; D006961:Hyperparathyroidism / Q000188:drug therapy*; D006965:Hyperplasia; D010279:Parathyroid Diseases / Q000378:metabolism; D010280:Parathyroid Glands / Q000473:pathology; D010282:Parathyroid Neoplasms / Q000378:metabolism*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000627:therapeutic use*
D014807:Vitamin D; C104450:25-hydroxyvitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase