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W Abbink, X M Hang, P M Guerreiro, F A T Spanings, H A Ross, A V M Canario, and G Flik

( Guerreiro et al. 2002 , Bevelander et al. 2006 ) and calcium regulation ( Guerreiro et al. 2001 , Abbink et al. 2004 , 2006 , Fuentes et al. 2006 ). Vitamin D is not synthesized by fish through photo-chemical processes in the skin and

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Jui-Cheng Hsieh, Rudolf C Estess, Ichiro Kaneko, G Kerr Whitfield, Peter W Jurutka, and Mark R Haussler

Introduction Molecular control of the mammalian hair cycle is incompletely characterized. Three gene products that are involved in this process are hairless (HR), the vitamin D receptor (VDR), and retinoid X receptor-α (RXRα). Loss

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Kevin J P Ryan, Zoe C T R Daniel, Lucinda J L Craggs, Tim Parr, and John M Brameld

Introduction Vitamin D (VitD) is a key nutrient for maintaining the health of the musculoskeletal system, with VitD deficiency leading to myopathy, classically characterised by hypotonia, weakness and atrophy of skeletal muscle, and a deterioration

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E P S Conceição, E G Moura, A C Manhães, J C Carvalho, J L Nobre, E Oliveira, and P C Lisboa

). Conversely, some studies have shown that, despite the classical role of vitamin D on bone metabolism, this hormone has nonclassic functions in inflammatory pathways, cellular proliferation and differentiation ( Omdahl et al. 2002 ), as well as in adipocyte

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Jorge N Artaza and Keith C Norris

2008 , Kovesdy et al . 2008 , Wang et al . 2008 ). The biologic pathways through which these effects are mediated remain poorly understood, but may be linked to vitamin D regulation of related fibrotic pathways ( Repo et al . 2007 ). Fibrosis

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Anthony M Belenchia, Sarah A Johnson, Mark R Ellersieck, Cheryl S Rosenfeld, and Catherine A Peterson

Introduction Vitamin D deficiency (VDD) is a global health concern for pregnant women, with prevalence rates as high as 84% in some populations ( Sachan et al . 2005 ). Given the strong association between maternal serum and placental

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Ana María Pino, Juan Manuel Rodríguez, Susana Ríos, Pablo Astudillo, Laura Leiva, Germán Seitz, Mireya Fernández, and J Pablo Rodríguez

regulation of aromatase expression has been studied mainly at the transcriptional level, showing that dexamethasone, vitamin D, testosterone and phytoestrogen genistein, among others, may function as regulatory factors of CYP19 expression ( Tanaka et al

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Liat Abovich Gilad, Oren Tirosh, and Betty Schwartz

Introduction We previously demonstrated that 17β-estradiol (E2) regulates the transcription and expression of vitamin D receptor (VDR) in vivo in rat colonocytes ( Schwartz et al. 2000 ) and duodenocytes ( Liel et al. 1999

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M. Hewison

Recent studies have shown that the hormonal form of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol), can affect both tissues and cells that are not directly involved in calcium homeostasis. In particular, a role for calcitriol as a regulator of immune cell differentiation and proliferation has been proposed. Specific high-affinity intracellular receptors for calcitriol (VDR) are detectable in activated T cells, and activated macrophages are able to synthesize calcitriol. A possible paracrine mechanism of action has been postulated. Vitamin D may therefore have a similar role to that of other immune regulatory molecules such as cytokines. The precise interaction of calcitriol with the cytokine network is not yet fully defined, but its ability to modulate immune cells in vitro and its association with inflammatory diseases are now well documented. These findings are outlined in this review with particular reference to effects on macrophages and lymphocytes.

Ectopic production of calcitriol

Initial evidence

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R. Buffenstein, I. N. Sergeev, and J. M. Pettifor


The vitamin D hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is generated by a series of hydroxylation steps in the liver and kidneys. We investigated whether naturally vitamin D-deficient subterranean mammals (naked mole rats, Heterocephalus glaber) employ the same enzymatic pathways, and whether these are regulated in a similar manner to that established for other mammals.

Vitamin D3-25-hydroxylase in the liver and both 25-hydroxyvitamin D3-l-hydroxylase and 25-hydroxyvitamin D3-24 hydroxylase (1-OHase and 24-OHase) in the kidney were detectable in mole rats. As expected for vitamin D-deficient mammals, the 1-OHase activity predominated over the 24-OHase. After mole rats received a supraphysiological supplement of vitamin D3, 1-OHase activity was suppressed and 24-OHase activity was enhanced. Irrespective of vitamin D status, forskolin (a protein kinase A activator) and dibutyryl cyclic AMP did not alter the activity of either 1-OHase or 24-OHase. These findings suggest that the response of renal hydroxylases to parathyroid hormone was blunted. Phorbol esters, 12-O-tetradecanoylphorbol 13-acetate (TPA) and 1-oleoyl-2-acetylglycerol (OAG) (protein kinase C activators), suppressed 1-OHase activity. 24-OHase activity was induced by TPA but not by OAG. These effects were similar to those illicited by vitamin D3 supplementation but were additive in that they increased the responses shown in vitamin D-replete mole rats.

These data confirm that naturally vitamin D-deficient mole rats can convert vitamin D3 to the hormone, 1,25(OH)2D3. Furthermore, the enzymes 1-OHase and 24-OHase present in the kidneys of these mammals are regulated independently by 1,25(OH)2D3 and protein kinase C-mediated pathways of intracellular signalling, but are not regulated by the cyclic AMP–protein kinase A signal transduction pathway.

Journal of Endocrinology (1993) 138, 59–64