This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Segersten, U. Articles by Westin, G. Search for Related Content PubMed PubMed Citation Articles by Segersten, U. Articles by Westin, G. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Medline Plus Health Information Parathyroid Disorders

25-Hydroxyvitamin D₃-1-Hydroxylase Expression in Normal and Pathological Parathyroid Glands

Department of Surgical Sciences, Endocrine Unit, Uppsala University Hospital, SE-751 85 Uppsala, Sweden

Address all correspondence and requests for reprints to: Gunnar Westin, Ph.D., Department of Surgical Sciences, Endocrine Unit, Uppsala University Hospital, Klinisk forskningsavdelning 2, ingang 70, plan 3, lab 9, SE-751 85 Uppsala, Sweden. E-mail: . gunnar.westin{at}surgsci.uu.se

Abstract

Active vitamin D, 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], plays a pivotal role in calcium homeostasis and bone metabolism. Circulating levels of 1,25(OH)₂D₃ are thought to be dependent mainly on the activity of the renal cytochrome P450 enzyme 25-hydroxyvitamin D₃-1-hydroxylase (1-hydroxylase), which is potently induced by PTH. However, 1-hydroxylase activity or expression has also been reported at several extrarenal sites, at which local synthesis of 1,25(OH)₂D₃ appears to fulfill autocrine or paracrine functions. This includes tissues such as placenta and brain that also express LRP-2/megalin, an endocytic receptor for multiple ligands, which is involved in the renal uptake of the substrate for 1 -hydroxylase, 25-hydroxyvitamin D₃. We have previously demonstrated LRP-2/megalin in parathyroid cells, and here we present results from RT-PCR and immunohistochemical analyses showing coincident expression of 1-hydroxylase in normal and pathological parathyroid tissue. With real-time quantitative RT-PCR analysis, the expression of 1-hydroxylase mRNA was higher in the majority of parathyroid adenomas and secondary hyperplastic glands but lower in parathyroid carcinomas, compared with normal parathyroid tissue. The findings imply that in addition to feedback control by circulating 1,25(OH)₂D₃ levels, parathyroid cells may also be influenced by local 1 -hydroxylase activity with possible growth regulatory and differentiating effects.

This article has been cited by other articles:

				J. L. Carter, S. E. O'Riordan, G. L. Eaglestone, M. P. Delaney, and E. J. Lamb Bone mineral metabolism and its relationship to kidney disease in a residential care home population: a cross-sectional study Nephrol. Dial. Transplant., November 1, 2008; 23(11): 3554 - 3565. [Abstract] [Full Text] [PDF]

				A. W Norman From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health Am. J. Clinical Nutrition, August 1, 2008; 88(2): 491S - 499S. [Abstract] [Full Text] [PDF]

				E. Romagnoli, M. L. Mascia, C. Cipriani, V. Fassino, F. Mazzei, E. D'Erasmo, V. Carnevale, A. Scillitani, and S. Minisola Short and Long-Term Variations in Serum Calciotropic Hormones after a Single Very Large Dose of Ergocalciferol (Vitamin D2) or Cholecalciferol (Vitamin D3) in the Elderly J. Clin. Endocrinol. Metab., August 1, 2008; 93(8): 3015 - 3020. [Abstract] [Full Text] [PDF]

				T. Krajisnik, P. Bjorklund, R. Marsell, O. Ljunggren, G. Akerstrom, K. B Jonsson, G. Westin, and T. E Larsson Fibroblast growth factor-23 regulates parathyroid hormone and 1{alpha}-hydroxylase expression in cultured bovine parathyroid cells J. Endocrinol., October 1, 2007; 195(1): 125 - 131. [Abstract] [Full Text] [PDF]

				K. Zajickova, J. Vrbikova, L. Canaff, P. D. Pawelek, D. Goltzman, and G. N. Hendy Identification and Functional Characterization of a Novel Mutation in the Calcium-Sensing Receptor Gene in Familial Hypocalciuric Hypercalcemia: Modulation of Clinical Severity by Vitamin D Status J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2616 - 2623. [Abstract] [Full Text] [PDF]

				K. Shiizaki, N. Hayakawa, I. Imazeki, I. Hatamura, T. Okada, S. Negi, T. Sakaguchi, T. Shigematsu, and T. Akizawa Binding of highly concentrated maxacalcitol to the nuclear vitamin D receptors of parathyroid cells Nephrol. Dial. Transplant., April 1, 2007; 22(4): 1078 - 1086. [Abstract] [Full Text] [PDF]

				A. Fournier, L. Harbouche, J. Mansour, and I. Shahapuni Impact of calcium and vitamin D therapy on arterial and cardiac disease in young adults with childhood-onset end stage renal disease Nephrol. Dial. Transplant., March 1, 2007; 22(3): 956 - 957. [Full Text] [PDF]

				P. Bjorklund, G. Akerstrom, and G. Westin Accumulation of Nonphosphorylated {beta}-Catenin and c-myc in Primary and Uremic Secondary Hyperparathyroid Tumors J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 338 - 344. [Abstract] [Full Text] [PDF]

				M. van Driel, M. Koedam, C. J. Buurman, M. Hewison, H. Chiba, A. G. Uitterlinden, H. A. P. Pols, and J. P. T. M. van Leeuwen Evidence for auto/paracrine actions of vitamin D in bone: 1{alpha}-hydroxylase expression and activity in human bone cells FASEB J, November 1, 2006; 20(13): 2417 - 2419. [Abstract] [Full Text] [PDF]

				J.-F. Bonne, J. Mansour, I. S. Philippe Moriniere, and A. Fournier Current treatment options in secondary renal hyperparathyroidism Nephrol. Dial. Transplant., October 1, 2006; 21(10): 2987 - 2989. [Full Text] [PDF]

				B Moosgaard, P Vestergaard, L Heickendorff, F Melsen, P Christiansen, and L Mosekilde Plasma 25-hydroxyvitamin D and not 1,25-dihydroxyvitamin D is associated with parathyroid adenoma secretion in primary hyperparathyroidism: a cross-sectional study. Eur. J. Endocrinol., August 1, 2006; 155(2): 237 - 244. [Abstract] [Full Text] [PDF]

				D. D. Bikle For Whom the Bugs Toll; They Toll for D IBMS BoneKEy, April 1, 2006; 3(4): 12 - 15. [Abstract] [Full Text] [PDF]

				K. Khadzkou, P. Buchwald, G. Westin, H. Dralle, G. Akerstrom, and P. Hellman 25-Hydroxyvitamin D3 1{alpha}-Hydroxylase and Vitamin D Receptor Expression in Papillary Thyroid Carcinoma J. Histochem. Cytochem., March 1, 2006; 54(3): 355 - 361. [Abstract] [Full Text] [PDF]

				A. Grey, J. Lucas, A. Horne, G. Gamble, J. S. Davidson, and I. R. Reid Vitamin D Repletion in Patients with Primary Hyperparathyroidism and Coexistent Vitamin D Insufficiency J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2122 - 2126. [Abstract] [Full Text] [PDF]

				K. N. Evans, H. Taylor, D. Zehnder, M. D. Kilby, J. N. Bulmer, F. Shah, J. S. Adams, and M. Hewison Increased Expression of 25-Hydroxyvitamin D-1{alpha}-Hydroxylase in Dysgerminomas: A Novel Form of Humoral Hypercalcemia of Malignancy Am. J. Pathol., September 1, 2004; 165(3): 807 - 813. [Abstract] [Full Text] [PDF]

				S. Komuro, M. Sato, and H. Kanamaru DISPOSITION AND METABOLISM OF F6-1{alpha},25(OH)2 VITAMIN D3 AND 1{alpha},25(OH)2 VITAMIN D3 IN THE PARATHYROID GLANDS OF RATS DOSED WITH TRITIUM-LABELED COMPOUNDS Drug Metab. Dispos., August 1, 2003; 31(8): 973 - 978. [Abstract] [Full Text] [PDF]

				M. F. Holick The Parathyroid Hormone D-Lema J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3499 - 3500. [Full Text] [PDF]

				R. Vieth, Y. Ladak, and P. G. Walfish Age-Related Changes in the 25-Hydroxyvitamin D Versus Parathyroid Hormone Relationship Suggest a Different Reason Why Older Adults Require More Vitamin D J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 185 - 191. [Abstract] [Full Text] [PDF]

				D. A. Hanley Puzzling vitamin D results Can. Med. Assoc. J., October 15, 2002; 167(8): 849 - 850. [Full Text] [PDF]