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-Hydroxylase1
Division of Medical Sciences, University of Birmingham, Birmingham, United Kingdom B15 2TH
Address all correspondence and requests for reprints to: Dr. Martin Hewison, Division of Medical Sciences, Queen Elizabeth Hospital, University of Birmingham, Edgbaston, Birmingham, United Kingdom B15 2TH. E-mail: m.hewsion{at}bham.ac.uk
The mitochondrial enzyme 25-hydroxyvitamin
D3-1
-hydroxylase (1-hydroxylase) plays an important
role in calcium homeostasis by catalyzing synthesis of the active form
of vitamin D, 1,25-dihydroxyvitamin D3, in the kidney.
However, enzyme activity assays indicate that 1-hydroxylase is also
expressed in a variety of extrarenal tissues; recent cloning of cDNAs
for 1-hydroxylase in different species suggests that a similar gene
product is found at both renal and extrarenal sites. Using specific
complementary ribonucleic acid probes and antisera to 1-hydroxylase,
we have previously reported the distribution of messenger ribonucleic
acid and protein for the enzyme along the mouse and human nephron. Here
we describe further immunohistochemical and Western blot analyses that
detail for the first time the extrarenal distribution of
1-hydroxylase in both normal and diseased tissues. Specific staining
for 1-hydroxylase was detected in skin (basal keratinocytes, hair
follicles), lymph nodes (granulomata), colon (epithelial cells and
parasympathetic ganglia), pancreas (islets), adrenal medulla, brain
(cerebellum and cerebral cortex), and placenta (decidual and
trophoblastic cells). Further studies using psoriatic skin highlighted
overexpression of 1-hydroxylase throughout the dysregulated stratum
spinosum. Increased expression of skin 1-hydroxylase was also
associated with sarcoidosis. In lymph nodes and skin from these
patients 1-hydroxylase expression was observed in cells positive for
the surface antigen CD68 (macrophages). The data presented here confirm
the presence of protein for 1-hydroxylase in several extrarenal
tissues, such as skin, placenta, and lymph nodes. The function of this
enzyme at novel extrarenal sites, such as adrenal medulla, brain,
pancreas, and colon, remains to be determined. However, the discrete
patterns of staining in these tissues emphasizes a possible role for
1-hydroxylase as an intracrine modulator of vitamin D function in
peripheral tissues.
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K. Yokomura, T. Suda, S. Sasaki, N. Inui, K. Chida, and H. Nakamura Increased Expression of the 25-Hydroxyvitamin D3-1{alpha}-Hydroxylase Gene in Alveolar Macrophages of Patients with Lung Cancer J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5704 - 5709. [Abstract] [Full Text] [PDF]
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J. Welsh, J. A. Wietzke, G. M. Zinser, B. Byrne, K. Smith, and C. J. Narvaez Vitamin D-3 Receptor as a Target for Breast Cancer Prevention J. Nutr., July 1, 2003; 133(7): 2425S - 2433. [Abstract] [Full Text] [PDF]
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 M. Hewison, L. Freeman, S. V. Hughes, K. N. Evans, R. Bland, A. G. Eliopoulos, M. D. Kilby, P. A. H. Moss, and R. Chakraverty Differential Regulation of Vitamin D Receptor and Its Ligand in Human Monocyte-Derived Dendritic Cells J. Immunol., June 1, 2003; 170(11): 5382 - 5390. [Abstract] [Full Text] [PDF]
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