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J Am Soc Nephrol 10:2465-2473, 1999
© 1999 American Society of Nephrology

Expression of 25-Hydroxyvitamin D3-1{alpha}-Hydroxylase in the Human Kidney

DANIEL ZEHNDER*, ROSEMARY BLAND*, ELIZABETH A. WALKER*, ARTHUR R. BRADWELL{dagger}, ALEXANDER J. HOWIE{ddagger}, MARTIN HEWISON* and PAUL M. STEWART*

* Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom.
{dagger} Division of Immunology and Infection, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom.
{ddagger} Department of Pathology, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom.

Correspondence to Dr. Paul M. Stewart, Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, United Kingdom. Phone: +44 121 627 2381; Fax: +44 121 627 2384; E-mail: P.M.Stewart{at}bham.ac.uk

Abstract. The secosteroid hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) plays a vital role in calcium metabolism, tissue differentiation, and normal bone growth. Biosynthesis of 1,25(OH)2D3 is catalyzed by the mitochondrial cytochrome P450 enzyme 25-hydroxyvitamin D3 1{alpha}-hydroxylase (1{alpha}-hydroxylase). Although activity of this enzyme has been described in several tissues, the kidneys are recognized to be the principal site of 1,25(OH)2D3 production. To date, enzyme activity studies using vitamin D-deficient animals have suggested that 1{alpha}-hydroxylase is expressed exclusively in proximal convoluted tubules. With the recent cloning of 1{alpha}-hydroxylase, specific cRNA probes and in-house polyclonal antiserum have been used to determine the distribution of 1{alpha}-hydroxylase along the human nephron. Immunohistochemistry and in situ hybridization studies indicated strong expression of 1{alpha}-hydroxylase protein and mRNA in the distal convoluted tubule, the cortical and medullary part of the collecting ducts, and the papillary epithelia. Lower expression was observed along the thick ascending limb of the loop of Henle and Bowman's capsule. Weaker and more variable expression of 1{alpha}-hydroxylase protein and mRNA was seen in proximal convoluted tubules, and no expression was observed in glomeruli or vascular structures. These data show for the first time the distribution of 1{alpha}-hydroxylase expression in normal human kidney. In contrast to earlier enzyme activity studies conducted in vitamin D-deficient animals, our data indicate that the distal nephron is the predominant site of 1{alpha}-hydroxylase expression under conditions of vitamin D sufficiency.




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