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Byline: Sanjay. Singh, Bandana. Jha, Narendra. Tiwary, Neeraj. Agrawal Background: Use of sunscreens on the face is becoming popular, and patients with melasma are prescribed sunscreen for use on the [...]

Both high and low vitamin D statuses have been associated with lower memory function. Apolipoprotein E (APOE) ζ4 alleles have been associated with reduced memory function, and separately with higher vitamin D concentrations. This report aims to examine if the presence of APOE ζ4 alleles contributes to the relationship between vitamin D and memory function. A total of 4848 (46% female) participants from the 1958 British birth cohort had information on APOE genotypes and completed memory tests at 50 years, where 4644 also had 25-hydroxyvitamin D (25(OH)D) concentrations measured at 45 years. Both low and high 25(OH)D concentrations were associated with lower memory function after adjustment for number of APOE ζ4 alleles ([P.sub.curvature] = 0.02). There was evidence of interaction between APOE ζ4 and 25(OH)D, suggesting the association between 25(OH)D concentrations and memory function is different for those with two APOE ζ4 alleles compared with those with zero or one APOE ζ4 alleles (recessive model [P.sub.interaction] = 0.01). Among participants with two APOE ζ4 alleles, higher 25(OH)D concentrations were associated with higher memory function, whereas in others, memory scores were slightly lower for individuals with higher versus lower concentrations. Further studies are required to replicate these findings. European Journal of Clinical Nutrition (2015) 69, 505-508; doi: 10.1038/ejcn.2014.201; published online 8 October 2014, INTRODUCTION Studies identify numerous modifiable lifestyle factors that are associated with cognitive function in the general adult population. (1, 2) One such factor is vitamin D, whereby deficiency has been [...]

BACKGROUND/OBJECTIVES: This study explored the association between serum 25-hydroxyvitamin D (25(OH)D) or parathyroid hormone (PTH) concentrations and the risk of metabolic syndrome (MetS) in middle-aged and older Korean adults using the most recent, nationally representative survey data. SUBJECTS/METHODS: The study sample consisted of 2624 Korean adults ([greater than or equal to]50 years old) who participated in the fifth Korean National Health and Nutrition Examination Surveys. Serum 25(OH)D was measured by radioimmunoassay and serum PTH was measured using chemiluminescence assay. MetS was defined according to the joint interim statement of the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. RESULTS: Serum 25(OH)D concentrations were significantly lower in subjects with MetS than in subjects without MetS, and the prevalence of MetS significantly decreased according to quartiles of serum 25(OH)D concentration. Serum 25(OH)D concentrations were negatively associated with the risk of elevated blood pressure (P for trend = 0.039), hypertriglyceridemia (P for trend = 0.0474) and reduced high-density lipoprotein cholesterol (P for trend = 0.0139), whereas serum PTH concentrations were positively associated with the risk of elevated blood pressure (P for trend = 0.0002) after adjusting for age, gender, residential district, education level, income, smoking status, body mass index, alcohol intake and physical activity. Furthermore, serum 25(OH)D concentrations were inversely associated with the risk of MetS after adjusting for confounding factors (P for trend =0.0163). However, serum PTH concentrations were not associated with the risk of MetS. CONCLUSION: Serum 25(OH)D concentration may be an independent risk factor of MetS among middle-aged and older Korean adults. European Journal of Clinical Nutrition (2015) 69, 425-430; doi: 10.1038/ejcn.2014.192;published online 24 September 2014, INTRODUCTION Vitamin D is a fat-soluble vitamin that can be produced in the skin following sun exposure, or ingested through diet and supplementation. Evidence suggests that 25-hydroxyvitamin D (25(OH) D), [...]

Background The association between vitamin D receptor (VDR) polymorphisms and asthma risk has been inconsistently investigated, but published studies demonstrated conflicting results. The aim of the current study was to investigate the impact of TaqI, BsmI, ApaI, and FokI VDR polymorphisms on asthma disease by using a meta-analysis approach. Methods Following the preferred reporting items for systematic reviews and meta-analyses guidelines, a systematic search and meta-analysis of the literature were conducted. Subgroup analyses were performed to detect potential sources of heterogeneity from selected study characteristics. Results A total of 2,097 cases and 1,968 controls in eight case-control studies were included in meta-analyses. A significant association was found between TaqI polymorphisms and asthma risk [OR 1.488 (95 % CI 1.019-2.174); P = 0.040] in a codominant model. In the same way, BsmI was significantly associated with asthma risk [OR 2.017 (95 % CI 1.236-3.851); P = 0.017] in the codominant model. The homozygote BB BsmI genotype was found to confer significant asthma risk. FokI polymorphism was marginally associated with asthma risk [OR 1.187 (95 % CI 0.975-1.446); P = 0.088] in the codominant model. In contrast, no significant association was found between ApaI polymorphism and asthma risk. Subgroup analyses revealed that gender and age modified significantly the association between FokI polymorphisms and asthma risk (P = 0.035 and 0.013, respectively). Publication year and serum 25(OH) D level tended, marginally, to moderate the association between FokI polymorphism and asthma risk. Conclusion TaqI, BsmI, and FokI VDR polymorphisms contribute to asthma susceptibility. The association between FokI polymorphism and asthma risk is influenced by study characteristics., Author(s): Kalthoum Tizaoui[sup.1] , Anissa Berraies[sup.1] [sup.2] , Besma Hamdi[sup.1] [sup.2] , Wajih Kaabachi[sup.1] , Kamel Hamzaoui[sup.1] , Agnès Hamzaoui[sup.1] [sup.2] Author Affiliations: (1) Department of Basic Sciences, Medicine Faculty [...]

Background/objectives In observational, but not interventional, studies there are strong associations between serum 25-hydroxyvitamin D (25(OH)D) and serum lipids. The purpose of the present study was to examine potential causes of this association. Subjects/methods A total of 17,411 subjects participating in the seventh survey of the Tromsø Study were included in the cross-sectional study; 5384 subjects who participated in both the sixth and seventh survey were included in the longitudinal study; 2365 subjects who participated in both the fourth and seventh survey were included in the genetic study; and 479 subjects with impaired glucose tolerance were included in the vitamin D binding protein (DBP) analyses. Results For serum 25(OH)D, there were strong and positive associations with LDL-, HDL-, and total-cholesterol, and a negative association with triglycerides that remained after adjustment for gender, age, BMI, diet, supplements, and lifestyle factors. These associations were seen in winter as well as summer. Except for serum cholesterol, change of season for blood sampling did not affect lipid levels. However, when analyzing separately, subjects with low or no intake of vitamin D supplements, fish oil and fat fish, only the association between 25(OH)D and HDL-cholesterol remained significant. Serum DBP or single-nucleotide polymorphisms related to 25(OH)D had no relation to lipid levels. Conclusions The associations between 25(OH)D and lipids (except for HDL-cholesterol) can be explained by known confounding factors. However, for HDL-cholesterol, the cause of the association with 25(OH)D still remains unknown., Author(s): Rolf Jorde [sup.1] [sup.2] , Guri Grimnes [sup.1] [sup.2] Author Affiliations: (1) Tromsø Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway (2) [...]

Pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) is the cornerstone of renoprotective therapy, and the reduction of persistent RAAS activation is considered to be an important target in the treatment of chronic kidney disease (CKD). Vitamin D is a steroid hormone that controls a broad range of metabolic and cell regulatory functions. It acts as a transcription factor and can suppress the renin gene, thereby acting as a negative endocrine regulator of RAAS. RAAS activation can reduce renal Klotho expression, and the Klotho-fibroblast growth factor 23 interaction may further reduce the production of active vitamin D. Results from both clinical and experimental studies suggest that vitamin D therapy is associated with a reduction in blood pressure and left ventricular hypertrophy and improves cardiovascular outcomes. In addition, a reduction in angiotensin II through RAAS blockade may have anti-proteinuric and anti-fibrotic effects. Vitamin D has also been shown to modulate the immune system, regulate inflammatory responses, improve insulin sensitivity and reduce high-density lipoprotein cholesterol. Taken together, these pleiotropic effects of vitamin D may slow down the progression of CKD. In this review, we discuss the experimental and early clinical findings that suggest a renoprotective effect of vitamin D, thereby providing an additional rationale beyond mineral metabolism for the close monitoring of, and supplemention with vitamin D from the earliest stages of CKD. Keywords Chronic kidney disease * Cardiovascular disease * 25-Hydroxyvitamin D [25(OH)D] * 1,25-Dihydroxyvitamin D [1,25[(OH).sub.2]D], Introduction There is a growing awareness that vitamin D has far-reaching effects beyond its role in calcium homeostasis [1-3]. The results from several studies suggest that vitamin D analogues improve [...]

Serum calcium levels are tightly controlled by an integrated hormone-controlled system that involves active vitamin D [1,25[(OH).sub.2]D], which can elicit calcium mobilization from bone when intestinal calcium absorption is decreased. The skeletal adaptations, however, are still poorly characterized. To gain insight into these issues, we analyzed the consequences of specific vitamin D receptor (Vdr) inactivation in the intestine and in mature osteoblasts on calcium and bone homeostasis. We report here that decreased intestinal calcium absorption in intestine-specific Vdr knockout mice resulted in severely reduced skeletal calcium levels so as to ensure normal levels of calcium in the serum. Furthermore, increased 1,25[(OH).sub.2]D levels not only stimulated bone turnover, leading to osteopenia, but also suppressed bone matrix mineralization. This resulted in extensive hyperosteoidosis, also surrounding the osteocytes, and hypomineralization of the entire bone cortex, which may have contributed to the increase in bone fractures. Mechanistically, osteoblastic VDR signaling suppressed calcium incorporation in bone by directly stimulating the transcription of genes encoding mineralization inhibitors. Ablation of skeletal Vdr signaling precluded this calcium transfer from bone to serum, leading to better preservation of bone mass and mineralization. These findings indicate that in mice, maintaining normocalcemia has priority over skeletal integrity, and that to minimize skeletal calcium storage, 1,25[(OH).sub.2]D not only increases calcium release from bone, but also inhibits calcium incorporation in bone., Introduction Ionized serum calcium levels are critical for the correct functioning of multiple vital cellular processes. Accordingly, the regulation of calcium homeostasis is directed at maintaining serum calcium levels within [...]

Disparities in longitudinal growth within a species can be partly explained by endocrinological differences. We hypothesized that regulatory networks acting locally in the growth plate may also be important. We tested this hypothesis by evaluating the IGF/IGFBP expression, the vitamin D pathway, and the PTHrP-Indian hedgehog (IHH) feedback loop in rib growth plates from 10- and 21-wk-old small- (Miniature Poodles, MP) and large-breed dogs (Great Danes, GD) using immunohistochemistry and quantitative (q)PCR. The rib growth plates of GD were 1.7 times thicker compared with those of MP, with larger proliferative (in absolute terms) and larger hypertrophic (in absolute and relative terms) zones. IGF/IGFBP gene expression profiling of the growth plates revealed decreased gene expression of igfbp2, -4, and -6 and an unaltered expression of igf-I and igf-II and their respective receptors in GD vs. MP. Immunohistochemistry and qPCR findings showed that the vitamin D pathway was more active in GD than in MP. Staining for 1[alpha]- and 24-hydroxylase was more abundant and intense in GD and the gene expressions of 1[alpha]-hydroxylase and the vitamin D receptor-driven 24-hydroxylase were six- and eightfold higher in GD vs. MP, respectively. Consistent with the immunohistochemistry findings, the expression of mRNA for components of the parathyroid hormone-related peptide (PTHrP)-IHH loop was different in GD compared with MP, with there being a relative threefold downregulation of Pthrp and a tenfold upregulation of Ihh in GD vs MP. These differences suggest that the effects of IHH in the regulation of chondrocyte proliferation and hypertrophy, both independently of PTHrP, can become more dominant during rapid growth rates. In conclusion, our data suggest that, in addition to modest endocrine differences, more pronounced changes in the expression of locally acting regulatory networks, such as the IGF system, vitamin D pathway, and PTHrP-IHH feedback loop are important contributors to within-species disparities in growth rates. canine; growth plate; vitamin D; Indian hedgehog; parathyroid hormone-related peptide; insulin-like growth factor doi: 10.1152/ajpendo.00170.2010.

N-methyl-D-aspartate (NMDA) receptors (NMDAR) are tetrameric amino acid receptors that act as membrane calcium channels. The presence of the receptor has been detected in the principal organs responsible for calcium homeostasis (kidney, bone, and parathyroid gland), pointing to a possible role in mineral metabolism. The aim of this study was to test the effect of NMDAR activation in the kidney and on 1,25[(OH).sub.2][D.sub.3] synthesis. We determined the presence of NMDAR subunits in HK-2 (human kidney cells) cells and proved its functionality. NMDA treatment for 4 days induced a decrease in 1[alpha]-hydroxylase levels and 1,25[(OH).sub.2][D.sub.3] synthesis through the activation of the MAPK/ERK pathway in HK-2 cells. In vivo administration of NMDA for 4 days also caused a decrease in blood 1,25[(OH).sub.2][D.sub.3] levels in healthy animals and an increase in blood PTH levels. This increase in PTH induced a decrease in the urinary excretion of calcium and an increase in urinary excretion of phosphorous and sodium as well as in diuresis. Bone turnover markers also increased. Animals with 5/6 nephrectomy showed low levels of renal 1[alpha]-hydroxylase as well as high levels of renal glutamate compared with healthy animals. In conclusion, NMDAR activation in the kidney causes a decrease in 1,25[(OH).sub.2][D.sub.3] synthesis, which induces an increase on PTH synthesis and release. In animals with chronic kidney disease, high renal levels of glutamate could be involved in the downregulation of 1[alpha]-hydroxylase expression. parathyroid hormone; mitogen-activated protein kinase; hyperparathyroidism doi: 10.1152/ajpendo.00428.2010.

The purpose of this study was to investigate whether diets differing in Ca concentration would have an influence on vitamin D (VitD) receptor (VDR) and calbindin D9k (Calb9k) immunoreactivities in the gastrointestinal tract of growing goats. In addition, the effect of a single VitD injection was studied, to clarify whether exogenous VitD would further increase the active Ca absorption mechanisms. The hypothesis of the study was that reduced Ca intake would lead to greater active Ca absorption, and with that, to greater amounts of VDR and Calb9k immunoreactivities. The normal Ca kid group (according to age requirements) received 2.5 to 6 g of Ca/d, whereas the lesser Ca kid group (less than requirements) received 1.5 to 4 g of Ca/d from wk 6 (weaning) to 15 (slaughter). In addition, 5 and 6 goat kids, respectively, of each group (normal Ca kid group, lesser Ca kid group), were injected with VitD (0.05 mg of cholecalciferol/kg of BW) in wk 14 of life. Blood samples were taken in wk 14 and 15. Calcium and VitD (25-hydroxyvitamin D and 1,25-dihydroxyvitamin D) concentrations were determined in serum. Immediately after slaughter, the duodenum (DD) and rumen (RU) were mounted in conventional Ussing chambers. Unidirectional flux rates of Ca across gastrointestinal tissues were measured. Additionally, tissue specimens of the gastrointestinal tract were collected, and formaldehyde-fixed paraffin sections were used for VDR and Calb9k immunohistochemistry. In all kid groups, a net absorption in the RU and a net secretion of Ca in the DD were observed. Immunoreactions of VDR were greatest in the duodenal mucosa, whereas Calb9k immunoreactions were observed in the forestomach and intestinal tissues. The greatest expression was observed in the duodenal surface epithelium. Additionally, in the VitD-injected groups, an immuno-reaction occurred in the jejunal superficial and basal glands and the ileal superficial epithelium. In contrast, the other groups showed no Calb9k immunoreactions at these sites. In conclusion, there is clear evidence for the RU as a main site for Ca absorption. The results of this study also indicate that VDR and Calb9k are highly expressed in the duodenal mucosa. The active absorption may not have such an important role in the DD because active transport was also evident in the RU. However, Calb9k expression seems to be stimulated by VitD administration. Key words: calbindin D9k, calcium, goat, vitamin D, vitamin D receptor doi: 10.2527/jas.2009-2682

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jada.2010.07.007 Byline: Cheryl D. Toner, Cindy D. Davis, John A. Milner Abstract: The case for the influence of vitamin D on health, including cancer prevention, is increasingly compelling. While some are calling for increases in the Tolerable Upper Intake Level, fortification, and dietary supplementation, questions regarding dose and individual response variability continue to merit attention. Colorectal cancer risk reduction with adequate vitamin D status is well documented. Protection has also been observed for cancer at all sites, skin, prostate, and breast. At the same time, some individuals may be adversely affected by elevated 25(OH)D concentrations with respect to risk of cancers of the prostate, breast, pancreas, and esophagus, and in some cases a U- or J-shaped association has been suggested. Future research should seek to clarify if and for whom there may be an increased risk for cancer at particular sites with high 25(OH)D concentrations, and the concentrations at which risk increases. Fundamentally, prospective longitudinal studies of these relationships are warranted. The health status, life stage, adiposity, estrogen exposure, and nutritional status of study participants should be taken into account. Continued investigation is necessary to ensure that vitamin D recommendations are appropriately targeted to individuals who stand to benefit most, while protecting vulnerable subgroups from risk of overexposure. Article History: Accepted 31 March 2010 Article Note: (footnote) Meets Learning Need Codes 2000, 2090, 5000, and 5150. To take the Continuing Professional Education quiz for this article, log in to ADA's Online Business Center at www.eatright.org/obc, click the "Journal Article Quiz" button, click "Additional Journal CPE Articles," and select this article's title from a list of available quizzes.

This study tests whether seasonal differences in the United States and European sunshine is associated with human birth patterns. Birth data are adjusted for 31-day months, leap years, and an annual percentage. Clear observations and birth indices are correlated for European and U.S. cities. With 2-month exposure to clearness, r-values are Chicago (0.63), Bismarck (0.81), Dallas (0.86), Thessaloniki (0.66), and Copenhagen (0.54) and, with 3-month exposure, Amsterdam (0.69). Peak clearness occurs during the autumn for the United States and spring/summer for Europe. Differences in clearness may explain birth pattern differences and reduced U.S. births in the 1930s. Although the effect of vitamin D is plausible, further research is required. DOI: 10.1080/19485565.2010.524093

In addition to its recognized role in bone health, recent studies point to vitamin D functions in other tissues, including the pancreas. We tested the association between the vitamin D status and glucose and lipid homeostasis in a school-based, cross-sectional survey of a representative sample of youth. We measured fasting plasma insulin, glucose, total cholesterol (TC), triglycerides (TG), HDL cholesterol (HDL-C) apolipoproteins (apo) A1 and B, and 25-hydroxyvitamin D [25(OH)D] concentrations in 878 boys and 867girls. The 25(OH)D concentrations (mean [+ or -] SD) were 45.9 [+ or -] 12.2 nmol/L in boys and 45.9 [+ or -] 13.0 nmol/L in girls. More than 93% of youth had suboptimal ( doi: 10.3945/jn.109.112250.

Valdivielso JM, Cannata-Andia J, Coll B, Fernandez E. A new role for vitamin D receptor activation in chronic kidney disease. Am J Physiol Renal Physiol 297: F1502-F1509, 2009. First published July 22, 2009; doi: 10.1152/ajprenal.00130.2009.--Vitamin D has proven to be much more than a simple 'calcium hormone.' The fact that the vitamin D receptor has been found in cells not related to mineral metabolism supports that statement. The interest of nephrologists in vitamin D and its effects beyond mineral metabolism has increased over the last few years, evidencing the importance of this so-called 'sunshine hormone.' In the present review, we highlight the most recent developments in the traditional use of vitamin D in chronic kidney disease (CKD) patients, namely, the control of secondary hyper- parathyroidism (sHPT). Furthermore, we also explore the data available regarding the new possible therapeutic uses of vitamin D for the treatment of other complications present in CKD patients, such as vascular calcification, left ventricular hypertrophy, or proteinuria. Finally, some still scarce but very promising data regarding a possible role of vitamin D in kidney transplant patients also are reviewed. The available data point to a potential beneficial effect of vitamin D in CKD patients beyond the control of mineral metabolism. doi: 10.1152/ajprenal.00130.2009

1[alpha],25[(OH).sub.2] vitamin D3 [1,25[(OH).sub.2][D.sub.3]] increases serum [Ca.sup.2+] concentration in vivo, an action counteracted by activation of the [Ca.sup.2+]-sensing receptor (CaSR), which decreases parathyroid hormone (PTH) secretion and increases renal [Ca.sup.2+] excretion. Relatively little is known of the role the CaSR plays in this response through its potentially direct actions in kidney, gut, and bone independently of PTH. We report PTH-independent roles of the CaSR in modulating the response to exogenous 1,25[(OH).sub.2][D.sub.3] in mice with targeted disruption of both the CaSR and PTH genes ([C.sup.-][P.sup.-]) compared with that in mice with disruption of the PTH gene alone ([C.sup.+][P.sup.-]) or wild-type mice ([C.sup.+][P.sup.+]). After intraperitoneal injection of 0.5 ng/g body wt 1,25[(OH).sub.2][D.sub.3], peak calcemic responses were observed at 24 h in all three genotypes in association with 1) a greater increase in serum [Ca.sup.2+] in [C.sup.-][P.sup.-] mice than in the other genotypes on a [Ca.sup.2+]-replete diet that was attenuated by a [Ca.sup.2+]-deficient diet and pamidronate, 2) increased urinary [Ca.sup.2+]-to-creatinine ratios (UCa/Cr) in the [C.sup.+][P.sup.-] and [C.sup.+][P.sup.+] mice but a lowered ratio in the [C.sup.-][P.sup.-] mice on a [Ca.sup.2+]-replete diet, and 3) no increase in calcitonin (CT) secretion in the [C.sup.+][P.sup.+] and [C.sup.+][P.sup.-] mice and a small increase in the [C.sup.-][P.sup.-] mice. PTH deficiency had the anticipated effects on the expression of key genes involved in [Ca.sup.2+] transport at baseline in the duodenum and kidney, and injection of 1,25[(OH).sub.2][D.sub.3] increased gene expression 8 h later. However, the changes in the genes evaluated did not fully explain the differences in serum [Ca.sup.2+] seen among the genotypes. In conclusion, mice lacking the full-length CaSR have increased sensitivity to the calcemic action of 1,25[(OH).sub.2][D.sub.3] in the setting of PTH deficiency. This is principally from enhanced 1,25[(OH).sub.2][D.sub.3]-mediated gut [Ca.sup.2+] absorption and decreased renal [Ca.sup.2+] excretion, without any differences in bone-related release of [Ca.sup.2+] or CT secretion among the three genotypes that could explain the differences in their calcemic responses. vitamin D; kidney

The possibility of pathological calcium metabolism is a critical health concern introduced by long-term space travel. Because vitamin D plays an important role in calcium homeostasis, we evaluated the effects of hypergravity on the expression of genes involved in vitamin D and calcium metabolism in ICR mice. When exposed to 2G hypergravity for 2 days, the mRNA expression of renal 25-hydroxyvitamin D 24-hydroxylase (Cyp24a1) was increased and that of 25-hydroxyvitamin D1[alpha]-hydroxylase (Cyp27b1) was decreased. Although hypergravity decreased food intake and increased the expression of starvation-induced genes, the changes in Cyp24a1 and Cyp27b1 expression were not due to starvation, suggesting that hypergravity affects these genes directly. Hypergravity decreased plasma 1[alpha], 25-dihydroxyvitamin [D.sub.3] levels in ICR mice, suggesting a consequence of decreased Cyp27b1 and increased Cyp24a1 expression. Although 1[alpha]-hydroxyvitamin [D.sub.3] [1[alpha](OH)[D.sub.3]] treatment induced the expression of vitamin D receptor (VDR) target genes in the kidney of 2G-exposed ICR mice to similar levels as controls, l[alpha](OH)[D.sub.3] increased the intestinal expression of Cyp24a1 in ICR mice. Hypergravity-dependent changes of Cyp24a1 and Cyp27b1 expression were diminished in mice exposed to hypergravity for 14 days, which may represent an adaptation to hypergravity stress. Hypergravity exposure also increased Cyp24a1 expression in the kidney of C57BL/6J mice. We examined the effects of hypergravity on VDR-null mice and found that renal Cyp27b1 expression in VDR-null mice was decreased by hypergravity while renal Cyp24a1 expression was not detected in VDR-null mice. Thus hypergravity modifies the expression of genes involved in vitamin D metabolism. vitamin D; vitamin D receptor; hypergravity; kidney; transcription

The active vitamin D metabolite 1[alpha],25-dihydroxyvitamin [D.sub.3] [1[alpha],25[(OH).sub.2][D.sub.3] has wide but not fully understood antitumor activity. A previous transcriptomic analysis of 1[alpha],25[(OH).sub.2][D.sub.3] action on human colon cancer cells revealed cystatin D (CST5), which encodes an inhibitor of several cysteine proteases of the cathepsin family, as a candidate target gene. Here we report that 1[alpha],25[(OH).sub.2][D.sub.3] induced vitamin D receptor (VDR) binding to, and activation of, the CST5 promoter and increased CST5 RNA and protein levels in human colon cancer cells. In cells lacking endogenous cystatin D, ectopic cystatin D expression inhibited both proliferation in vitro and xenograft tumor growth in vivo. Furthermore, cystatin D inhibited migration and anchorage-independent growth, antagonized the Wnt/[beta]-catenin signaling pathway, and repressed c-MYC expression. Cystatin D repressed expression of the epithelial-mesenchymal transition inducers SNAI1, SNAI2, ZEB1, and ZEB2 and, conversely, induced E-cadherin and other adhesion proteins. CST5 knockdown using shRNA abrogated the antiproliferative effect of 1[alpha],25[(OH).sub.2][D.sub.3], attenuated E-cadherin expression, and increased c-MYC expression. In human colorectal tumors, expression of cystatin D correlated with expression of VDR and E-cadherin, and loss of cystatin D correlated with poor tumor differentiation. Based on these data, we propose that CST5 has tumor suppressor activity that may contribute to the antitumoral action of 1[alpha],25[(OH).sub.2][D.sub.3] in colon cancer., Introduction There is an increasing interest in the active vitamin D metabolite 1[alpha],25-dihydroxyvitamin [D.sub.3] [1[alpha],25[(OH).sub.2][D.sub.3] and its analogs as preventive and therapeutic anticancer agents, and a number of clinical trials [...]

The active form of vitamin D, 1[alpha], 25-dihydroxyvitamin [D.sub.3] [1,25[(OH).sub.2][D.sub.3]], suppresses disease development in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). However, complete disease prevention only occurs with doses that dramatically elevate serum calcium levels, thus limiting the usefulness of 1,25[(OH).sub.2][D.sub.3] as a potential MS therapeutic agent. Because calcitonin (CT) is believed to be released by hypercalcemia and has been shown to be anti-inflammatory, we examined whether suppression of EAE by 1,25[(OH).sub.2][D.sub.3] could be mediated either in part or entirely by CT. Continuous administration of pharmacological doses of CT did not prevent EAE. However, a combination of CT and a subtherapeutic dose of 1,25[(OH).sub.2][D.sub.3] additively suppressed EAE without causing hypercalcemia. Moreover, CT decreased the dose of 1,25[(OH).sub.2][D.sub.3] required for disease suppression. Our results suggest that CT may be a significant factor but cannot account entirely for 1,25[(OH).sub.2][D.sub.3]-mediated suppression of EAE. calcium | calcium homeostasis | immune system | multiple sclerosis | vitamin D

The classic role of vitamin D has involved its function in calcium metabolism. However, a much broader perspective of the importance of vitamin D is now emerging. Therefore, a new approach is needed based on a combination of molecular biological, physiological, and clinical/epidemiological studies. The remarkable range of the effects of vitamin D relates to our new understanding of both the role of the vitamin D receptor and analyses of what might be considered an optimum vitamin D status in populations exposed to very different diets and levels of sun exposure. Assessing the breadth of the current approaches was the basis of the 22nd Marabou Symposium that took place in Stockholm in June 2007.

Objective: To analyze vitamin D status based on serum 25-hydroxyvitamin D (25OHD) measurements, its determinants and health correlates in a representative sample of German adults. Subjects: A total of 1763 men and 2267 women, 18- to 79-year old, who participated in the representative German National Health Interview and Examination Survey 1998 and the integrated German Nutrition Survey. Results: The median vitamin D intake from both diet and supplements did not meet the recommended level of 5 [micro]g/day, in either men (2.8[micro]g/day) or women (2.3[micro]g/day). Altogether 80.9% of men and 88.5% of women had vitamin D intakes below this level. Moderate (12.5-25 nmol/I serum 25OHD levels) and mild (25-50 nmol/I) vitamin D deficiency was prevalent in the adult population in Germany, even in younger age groups. Overall, 57% of men and 58% of women had vitamin D levels below 50 nmol/I. Among 65- to 79-year-old women, the proportion amounted to 75%, even during the sunnier half of the year. In sex-specific multiple linear regression models, independent determinants of serum 25OHD levels consistently included season, vitamin D intake from both diet and supplements, physical activity and living in a partnership. In addition, age and current menopausal hormone use contributed to the model among women, as opposed to time of day of blood sampling and body mass index (marginally) among men. Significantly lower serum 25OHD levels were observed in women with hypertension, cardiovascular diseases and noninsulin-treated diabetes mellitus as well as in men with insulin-treated diabetes mellitus compared with nonaffected participants. Conclusions: Vitamin D deficiency is a public health issue in Germany. We identified a number of determinants with potential for primary prevention of vitamin D deficiency. Risk and benefits of preventive actions need to be examined in further studies. doi:10.1038/sj.ejcn.1602825; published online 30 May 2007 Keywords: vitamin D; deficiency; serum 25OHD level; epidemiology; population survey; Germany, Introduction Vitamin D plays a vital role in maintenance of calcium homeostasis. Currently, in Europe and North America, rickets and osteomalacia, the clinical outcomes of a severe vitamin D deficiency, [...]

The available evidence suggests that vitamin D has cardiovascular effects besides regulating calcium homeostasis. To examine the effect of 1,25-dihydroxyvitamin D3, the major metabolite of vitamin D, on endothelium-dependent contractions, aortic rings of spontaneously hypertensive rats (SHR) were suspended in organ chambers for isometric force measurements. Rings were incubated with [N.sup.[omega]]-nitro-L-arginine methyl ester (LNAME) and then exposed to increasing concentrations of acetylcholine, ATP, or the calcium ionophore to trigger contractions. This was done in the absence or presence of 1,25-dihydroxyvitamin D3. The release of prostacyclin after acetylcholine or A-23187 stimulation was also measured. The cytosolic-free calcium concentration was measured by confocal microscopy after incubation with the fluorescent dyes fluo-4 and fura red. The presence of vitamin D receptors was confirmed using immunohistochemistry. Acetylcholine- and ATP-induced endothelium-dependent contractions were significantly reduced compared with those obtained in the absence of the drug. This effect was not present if A-23187 was used as an agonist. The acetylcholine- but not the A-23187-induced release of prostacyclin was reduced by the acute administration of 1,25-dihydroxyvitamin [D.sub.3]. Exposure to 1,25-dihydroxyvitamin D3 reduced the increase in cytosolic-free calcium concentration caused by acetylcholine but not by A-23187 in cells. Vitamin D receptors were densely distributed in the endothelium. Inecalcitol (19-nor-14-epi-23-yne-l,25-dihydroxy-vitamin [D.sub.3]), a synthetic analog of vitamin D, caused a comparable depression of endothelium-dependent contractions as 1,25-dihydroxy-vitamin D3. These results demonstrate that vitamin D3 modulates vascular tone by reducing calcium influx into the endothelial cells and hence decreasing the production of endothelium-derived contracting factors. calcium; endothelium-derived contracting factors; inecalcitol

Prospective studies suggest that dietary vitamin D may at least modestly reduce the risk of breast cancer. This review addresses issues raised by recent studies, including differences in findings related to dietary source of vitamin D, menopausal status, and tumor characteristics. It also discusses the optimal timing of vitamin D assessment. Key words: breast cancer, vitamin D, diet

BACKGROUND: Inadequate sun exposure and dietary vitamin D intake can result in vitamin D insufficiency. However, limited data are available on actual vitamin D status and predictors in healthy individuals in different regions and by season. METHODS: We compared vitamin D status [25-hydroxyvitamin D; 25(OH)D] in people < 60 years of age using data from cross-sectional studies of three regions across Australia: southeast Queensland (27[degrees]S; 167 females and 211 males), Geelong region (38[degrees]S; 561 females), and Tasmania (43[degrees]S; 432 females and 298 males). RESULTS: The prevalence of vitamin D insufficiency ([less than or equal to] 50 nmol/L) in women in winter/spring was 40.5% in southeast Queensland, 37.4% in the Geelong region, and 67.3% in Tasmania. Season, simulated maximum daily duration of vitamin D synthesis, and vitamin D effective daily dose each explained around 14% of the variation in 25(OH)D. Although latitude explained only 3.9% of the variation, a decrease in average 25(OH)D of 1.0 (95% confidence interval, 0.7-1.3) nmol/L for every degree increase in latitude may be clinically relevant. In some months, we found a high insufficiency or even deficiency when sun exposure protection would be recommended on the basis of the simulated ultraviolet index. CONCLUSION: Vitamin D insufficiency is common over a wide latitude range in Australia. Season appears to be more important than latitude, but both accounted for less than one-fifth of the variation in serum 25(OH)D levels, highlighting the importance of behavioral factors. Current sun exposure guidelines do not seem to fully prevent vitamin D insufficiency, and consideration should be given to their modification or to pursuing other means to achieve vitamin D adequacy. KEY WORDS: 25(OH)D, behavior, latitude, UV index, UVR, vitamin D, vitamin D index. Environ Health Perspect 115:1132-1139 (2007). doi:10.1289/ehp.9937 available via http://dx.doi.org/ [Online 17 April 2007], Most (90-100%) vitamin D is produced endogenously following solar ultraviolet radiation (UVR) of precursors within sun-exposed skin (Holick 1994). Only a few foods, such as oily fish, contain significant amounts [...]

A new, completely in vivo method of measuring the rate of intestinal phosphate absorption has been developed. As expected from previous in vitro and ex vivo measurements, intestinal phosphate absorption is potently and rapidly stimulated by 1,25-dihydroxyvitamin [D.sub.3]. The response is saturated with as little as 11.3 ng of 1,25-dihydroxyvitamin [D.sub.3] per day, consistent with a genomic mechanism. The effect of 1,25-dihydroxyvitamin [D.sub.3] disappears when the dosing solution of phosphate is at 2 M, suggesting that 1,25-dihydroxyvitamin D3 stimulates active transport of phosphate but not diffusion of phosphate. Finally, unlike findings resulting from in vitro or ex vivo experiments, no evidence in vivo was obtained that phosphate absorption requires sodium or is inhibited by potassium. vitamin D; phosphorus; intestine doi: 10.1152/ajpendo.00654.2006

The major physiological role of the vitamin D receptor (VDR) is the maintenance of mineral ion homeostasis. Mutation of the VDR, in humans and mice, results in alopecia. Unlike the effects of the VDR on mineral ion homeostasis, the actions of the VDR that prevent alopecia are ligand-independent. Although absence of the VDR does not prevent the development of a keratinocyte stem cell niche in the bulge region of the hair follicle, it results in an inability of these stem cells to regenerate the lower portion of the hair follicle in vivo and impairs keratinocyte stem cell colony formation in vitro. VDR ablation is associated with a gradual decrease in keratinocyte stem cells, accompanied by an increase in sebaceous activity, a phenotype analogous to that seen with impaired canonical Wnt signaling. Transient gene expression assays demonstrate that the cooperative transcriptional effects of [beta]-catenin and Lef1 are abolished in keratinocytes isolated from VDR-null mice, revealing a role for the unliganded VDR in canonical Wnt signaling. Thus, absence of the VDR impairs canonical Wnt signaling in keratinocytes and leads to the development of alopecia due to a defect in keratinocyte stem cells. alopecia | knockout | Wnt signaling | Lef

Applied to skin color, the sexual selection hypothesis proposes that male preference for light-skinned females explains the presence of light skin in areas of low solar radiation. According to this proposal, in areas of high solar radiation, natural selection for dark skin overrides the universal preference of males for light females. But in areas in which natural selection ceases to act, sexual selection becomes more important, and causes human populations to become light-skinned, and females to be lighter than males. The sexual selection hypothesis proposes that human sexual dimorphism of skin color should be positively correlated with distance from the equator. We tested the prediction that sexual dimorphism should increase with increasing latitude, using adult-only data sets derived from measurements with standard reflectance spectrophotometric devices. Our analysis failed to support the prediction of a positive correlation between increasing distance from the equator and increased sexual dimorphism. We found no evidence in support of the sexual selection hypothesis. KEY WORDS solar radiation; skin color; vitamin D

An essential element of the innate immune response to injury is the capacity to recognize microbial invasion and stimulate production of antimicrobial peptides. We investigated how this process is controlled [...]

The concept of fractal geometry is useful for the analysis of irregular and complex structures often seen in nature. Here we apply this concept to investigate the structural mechanism of the development of pulmonary emphysema in the klotho mouse, which, after milk feeding, exhibits characteristics resembling aging and develops emphysema. We calculated the relationships between perimeter and size characterizing shape and between cumulative frequency and size of the terminal air spaces identified from histologic slides and found that both relations followed a power law with fractal properties. However, the fractal dimensions related to the shape and size (Dsn) in the klotho mice were significantly lower than in controls. Additionally, in the klotho mice, Dsn decreased with age without significant change in mean linear intercept. These abnormal morphological changes were restored when the klotho mice were fed with a vitamin D-deficient diet. Previously undescribed morphological model simulations showed that a random destruction, in which the destruction process occurs homogeneously in the lungs, was more consistent with the data than a correlated destruction that is usually seen in smoking-related human emphysema. These results suggest that the pathological changes in the lungs of the klotho mice are derived not from localized causes, but from systemic causes that are related to abnormal activation of vitamin D. The morphogenesis of emphysema in the klotho mice and morphological analyses using fractal geometry may contribute to the understanding of the progressive nature and cause of parenchymal destruction in human emphysema. chronic obstructive pulmonary disease | fractal | lung | morphometry | simulation

The major circulating form of vitamin D is 25-hydroxycholecalciferol [25(OH)D3], which is delivered to target tissues in complex with the serum vitamin D binding protein (DBP). We recently observed that mammary cells can metabolize 25(OH)D3 to 1,25-dihydroxycholecalciferol [1,25[(OH).sub.2]D3], the vitamin D receptor (VDR) ligand, and the objective of our study was to elucidate the mechanisms by which the 25(OH)D3-DBP complex is internalized by mammary cells prior to metabolism. Using fluorescent microscopy and temperature-shift techniques, we found that T-47D breast cancer cells rapidly internalize DBP via endocytosis, which is blunted by receptor-associated protein, a specific inhibitor of megalinmediated endocytosis. Endocytosis of DBP was associated with activation of VDR by 25(OH)D3 but not 1,25[(OH).sub.2]D3 (as measured by induction of the VDR target gene, CYP24). We also found that megalin and its endocytic partner, cubilin, are coexpressed in normal murine mammary tissue, in nontransformed human mammary epithelial cell lines, and in some established human breast cancer cell lines. To our knowledge, our studies are the first to demonstrate that mammaryderived cells express megalin and cubilin, which contribute to the endocytic uptake of 25(OH)D3-DBP and activation of the VDR pathway.

The 2005 Dietary Guidelines for Americans recommend that older adults, people with dark skin, and those exposed to insufficient ultraviolet radiation (i.e., sunlight) consume extra vitamin D from vitamin D-fortified foods and/or supplements. Individuals in these high-risk groups should consume 25 [micro]g (1000 IU) of vitamin D daily to maintain adequate blood concentrations of 25-hydroxyvitamin D, the biomarker, for vitamin D status. This review considers recommendations for vitamin D-rich foods and dietary supplements, as well as specific problems with self-prescribing sun exposure or artificial sources of ultraviolet radiation to meet the vitamin D recommendations for older people. Key words: aging, Dietary Guidelines for Americans, older adults, sunlight, supplements, vitamin D doi: 10.1301/nr.2006.sept.410- 421

The balance between bioactivation and degradation of 1,25-dihydroxyvitamin [D.sub.3] [1,25[(OH).sub.2][D.sub.3]] is critical for ensuring appropriate biological effects of vitamin D. Cytochrome P450, family 24-mediated (CYP24-mediated) 24-hydroxylation of 1,25[(OH).sub.2][D.sub.3] is an [...]

Dihydroxycholecalciferol bound to its receptor functions as a potent antimitotic, prodifferentiating, proapoptotic hormone in different cell types and tissues. Epidemiological studies have linked low human serum concentrations of the vitamin D precursor hydroxycholecalciferol to colorectal cancer incidence. We have demonstrated in human colorectal tissue and cells the conversion of the precursor to dihydroxycholecalciferol, as well as the existence of the vitamin D catabolic pathway. These findings suggest a role for the colonic vitamin D system in tumor prevention. Low calcium intake has been found to be associated with human colorectal cancer incidence. In mice fed calcium equivalent to a low human intake, the degradative vitamin D pathway was increased, mainly in the ascending colon. Refeeding the mice high levels of vitamin D and calcium lowered tissue 25-hydroxycholecalciferol 24-hydroxylase activity, but only replenishment of folic acid normalized expression of the degradative pathway completely. Normalization occurred also when mice consuming low calcium diets were fed soy or the phytoestrogen genistein. These results indicate that colonic vitamin D synthesis is not only under stringent control of nutritional calcium, but also of folate, a methyl donor, which suggests epigenetic control of vitamin D hydroxylases. KEY WORDS: * colonic vitamin D hydroxylases * dietary calcium and folate * vitamin D degradation * phytoestrogens * epigenetic regulation

FGF23 suppresses both serum phosphate and 1,25-dihydroxyvitamin D [1,25D] levels in vivo. Because 1,25D itself is a potent regulator of phosphate metabolism, it has remained unclear whether FGF23-induced changes in phosphate metabolism were caused by a 1,25D-independent mechanism. To address this issue, we intravenously administered recombinant FGF23 to vitamin D receptor (VDR) null (KO) mice as a rapid bolus injection and evaluated the early effects of FGF23. Administration of recombinant FGF23 further decreased the serum phosphate level in VDR KO mice, accompanied by a reduction in renal sodium-phosphate cotransporter type IIa (NaPi2a) protein abundance and a reduced renal 25-hydroxyvitamin D-1[alpha]-hydroxylase (1[alpha]OHase) mRNA level. Thus FGF23-induced changes in NaPi2a and 1[alpha]OHase expression are independent of the 1,25D/VDR system. However, 24-hydroxylase (24OHase) mRNA expression remained undetectable by the treatment with FGF23. We also analyzed the regulatory mechanism for FGF23 expression. The serum FGF23 level was almost undetectable in VDR KO mice, whereas dietary calcium supplementation significantly increased circulatory levels of FGF23 and its mRNA abundance in bone. This finding indicates that calcium is another determinant of FGF23 production that occurs independently of the VDR-mediated mechanism. In contrast, dietary phosphate supplementation failed to induce FGF23 expression in the absence of VDR, whereas marked elevation in circulatory FGF23 was observed in wild-type mice fed with a high-phosphate diet. Taken together, FGF23 works, at least in part, in a VDR-independent manner, and FGF23 production is also regulated by multiple mechanisms involving VDR-independent pathways. VDR; phosphate metabolism; sodium phosphate cotransporter

This article provides a review of the evidence identifying the factors related to vitamin D status in adolescents. The prevalence of vitamin D deficiency based on 25-hydroxyvitamin D [25(OH)D] of KEY WORDS: * vitamin D * adolescents * bone density * bone accrual * parathyroid hormone

The NF-[kappa]B component RelB is essential for dendritic cell (DC) differentiation and maturation. The vitamin D receptor (VDR) is a nuclear receptor that mediates inhibition of DC maturation and transcriptional repression of relB after engagement of its ligand, 1[alpha],25-dihydroxyvitamin [D.sub.3], or related analogs ([D.sub.3] analogs). Ligand-dependent relB suppression was abolished by a histone deacetylase (HDAC) inhibitor. Constitutive association of VDR with the relB promoter was demonstrated in DCs by chromatin immunoprecipitation. Promoter binding by VDR was enhanced by ligand and reduced by LPS. Association of HDAC3 and HDAC1 with the relB VDR-binding site was observed, but only HDAC3 was reciprocally modulated by [D.sub.3] analog and LPS. Overexpression of HDAC3 caused relB promoter suppression, increased sensitivity to [D.sub.3] analog, and resistance to LPS. Depletion of HDAC3 attenuated relB suppression by [D.sub.3] analog. In vivo, [D.sub.3] analog resulted in reduced RelB in DCs from VDR WT mice but not VDR knockout mice. Other NF-[kappa]B family members were unaffected. In vivo RelB suppression was prevented by concomitant administration of HDAC inhibitor, which also resulted in up-regulation of RelB and c-Rel in control animals. We conclude that vitamin D-regulated relB transcription in DCs is controlled by chromatin remodeling by means of recruitment of complexes including HDAC3. NF-[kappa]B | antigen presentation | nuclear receptors | chromatin remodeling | immunity

Fibroblast growth factor-23 (FGF23) has been recently identified as playing an important pathophysiological role in phosphate homeostasis and vitamin D metabolism. To elucidate the precise physiological regulation of FGF-23, we characterized the mouse FGF-23 5'-flanking region and analyzed its promoter activity. The 5'-flanking region of the mouse FGF-23 gene contained a TFIID site (TATA box) and several putative transcription factor binding sites, including MZF1, GATA-1 and c-Ets-1 motifs, but it did not contain the typical sequences of the vitamin D response element. Plasmids encoding 554-bp (pGL/-0.6), 364-bp (pGL/-0.4) and 200-bp (pGL/-0.13) promoter regions containing the TFIID element and + 1-bp fragments drove the downstream expression of a luciferase reporter gene in transfection assays. We also found that FGF-23 mRNA was expressed in K-562 erythroleukemia cell lines but not in MC3T3-E1, Raji, or Hep G2 human carcinoma cells. Treatment with 1,25-dihydroxyvitamin [D.sub.3] in the presence of high phosphate markedly stimulated pGL/-0.6 activity, but calcium had no effect. In addition, the plasma FGF-23 levels were affected by the dietary and plasma inorganic phosphate concentrations. Finally, the levels of plasma FGF-23 in vitamin D receptor-null mice were significantly lower than in wild-type mice. The presents study demonstrated that vitamin D and the plasma phosphate level are important regulators of the transcription of the mouse FGF-23 gene. gene regulation; vitamin D receptor; phosphate homeostasis

Abstract We investigated the role of vitamin-D receptor gene (VDR) and calcitonin receptor (CTR) gene polymorphism in childhood nephrolithiasis in the north Indian population. A control group of 60 healthy [...]

An estimation of the effectiveness of vitamin D supplementation in preventing hip and nonvertebral fractures in older persons is presented. It was concluded that oral vitamin D supplementation between 700 to 800 IU/d appears to reduce the risk of hip and any nonvertebral fractures in ambulatory or institutionalized elderly persons.

Studies were performed to further characterize the male-specific hepatic recombinant microsomal vitamin D 25-hydroxlase CYP2C11, expressed in baculovirus-infected insect cells, and determine whether it is also a vitamin D 24-hydroxylase. 25- and 24-hydroxylase activities were compared with those of 10 other recombinant hepatic microsomal cytochrome P-450 enzymes expressed in baculovirus-infected insect cells. Each of them 25-hydroxylated vitamin [D.sub.2], vitamin [D.sub.3], 1[alpha]-hydroxyvitamin [D.sub.2] (1[alpha]OH[D.sub.2]), and 1[alpha]-hydroxyvitamin [D.sub.3] (1[alpha]OH[D.sub.3]). CYP2C11 had the greatest activity with these substrates, except vitamin [D.sub.3], which had the same activity as four of the other enzymes. The descending order of 25-hydroxylation by CYP2C11 was 1[alpha]OH[D.sub.3] > 1[alpha]OH[D.sub.2] > vitamin [D.sub.2] > vitamin [D.sub.3]. Each of the recombinant cytochrome P-450 enzymes 24-hydroxylated 1[alpha]OH[D.sub.2]. CYP2C11 had the greatest activity. 24-Hydroxylation of 1[alpha]OH[D.sub.3] was very low, and there was none with vitamin [D.sub.3]. Only CYP2C11 24-hydroxylated vitamin [D.sub.2]. Structures of vitamin D metabolites, including 24-hydroxyvitamin [D.sub.2], 1,24(S)-dihydroxyvitamin [D.sub.2], and 1,24-dihydroxyvitamin [D.sub.3], were confirmed by HPLC and. gas chromatography retention times and characteristic mass spectrometric fragmentation patterns. In male rats, hypophysectomy significantly reduced body weight, liver weight, hepatic CYP2C11 mRNA expression, and 24- and 25-hydroxylation of 1[alpha]OH[D.sub.2]. Expression of CYP2J3 and CYP2R1 mRNA did not change. In male rat hepatocytes, CYP2C11 mRNA expression and 24-and 25-hydroxylation were significantly reduced after culture for 24 h compared with uncultured cells. Expression of CYP2J3 and CYP2R1 either increased or did not change. It is concluded that CYP2C11 is a male-specific hepatic microsomal vitamin D 25-hydroxylase that hydroxylates vitamin [D.sub.2], vitamin [D.sub.3], 1[alpha]OH[D.sub.2], and 1[alpha]OH[D.sub.3]. CYP2C11 is also a vitamin D 24-hydroxylase. 25-hydroxyvitamin D; 24-hydroxyvitamin D; liver microsomes; cytochrome P-450 enzymes