Calcitonin, a Regulator of the 25-Hydroxyvitamin D3 1α-Hydroxylase Gene

Zhong, Yan; Armbrecht, H. J.; Christakos, Sylvia

doi:10.1074/jbc.m806561200

Cited by 61 publications

(60 citation statements)

References 58 publications

(76 reference statements)

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“…Since calcitonin levels as well as 1,25(OH) 2 D 3 levels are elevated during lactation, early studies suggested that calcitonin may have a role to stimulate CYP27B1 resulting in increased plasma 1,25(OH) 2 D 3 and increased intestinal calcium absorption during lactation when the need for calcium is increased (427). Studies have shown an effect of calcitonin on CYP27B1 transcription (521). In addition to calcitonin, prolactin, which is also elevated during lactation, has been reported to stimulate renal CYP27B1 (382).…”

Section: E Regulation Of Renal Cyp27b1 and Cyp24a1mentioning

confidence: 99%

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

Christakos

Dhawan

Verstuyf

et al. 2016

Physiological Reviews

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1,424

1,234

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, [1,25(OH) 2 D 3 ] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH) 2 D 3 action involves the direct binding of the 1,25(OH) 2 D 3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH) 2 D 3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH) 2 D 3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease.

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Section: E Regulation Of Renal Cyp27b1 and Cyp24a1mentioning

confidence: 99%

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

Christakos

Dhawan

Verstuyf

et al. 2016

Physiological Reviews

Self Cite

1,424

1,234

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“…147, 226 The feedback inhibition of 1a-hydroxylase by 1,25(OH) 2 D 3 is mostly due to inhibition of PTH and the cAMP pathways. 21 Plasma phosphate concentration is also involved in the control of 1,25(OH) 2 D 3 production.…”

Section: Biology Of Vitamin D Activation Of Vitamin Dmentioning

confidence: 99%

Vitamin D Metabolism and Rickets in Domestic Animals

2010

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Rickets and osteomalacia are increasing in prevalence in people because of cultural practices, breast-feeding, decreased sun exposure, and increased sunscreen usage. Several hereditary forms of rickets owing to either renal phosphate wasting or defects in vitamin D metabolism are also reported in people. Rickets is well recognized in domestic animals, but published reports are not always supported by microscopic findings, and diagnoses based on clinical signs and radiology are unreliable. Most cases in domestic animals are caused by dietary deficiency of either vitamin D or phosphorus, but occasional inherited forms are reported in pigs, sheep, cats, and dogs. There is variation between species in susceptibility to dietary vitamin D and phosphorus deficiency and in the ability to manufacture vitamin D in their skin. A number of mouse models have been discovered or created to study human skeletal diseases and skeletal homeostasis. With the discovery that vitamin D is involved in not only calcium and phosphorus homeostasis but also in the immune system and cancer, there is great potential for new and existing animal models to generate valuable information about vitamin D and its many functions. This review presents an overview of vitamin D metabolism and rickets in domestic and laboratory animals and makes comparisons where appropriate with the disease in humans. Keywords bone, rickets, vitamin D, phosphorus, genetic diseasesRickets is a classic metabolic bone disease of humans and animals, first described in the first and second centuries. 158,165 With the discovery that vitamin D could prevent rickets, the prevalence of this disease in developed countries plummeted; however, it still occurs. In fact, the prevalence of rickets and vitamin D insufficiency is increasing in people of all ages in the developed world, due in part to decreased sunlight exposure and widespread sunscreen usage. 88 The disease is well recognized in animals, but published reports are uncommon and sometimes confusing.The pathogenesis of rickets involves impaired mineralization of physeal and epiphyseal cartilage during endochondral ossification and of newly formed osteoid. Most cases in domestic animals are caused by dietary deficiency of either vitamin D or phosphorus, but occasional inherited forms are reported. 109,200 Osteomalacia is caused by a failure of newly formed osteoid to mineralize, but it occurs in adults after closure of growth plates. 109In this article, we review vitamin D metabolism and rickets, with reference to the disease in domestic animals but presenting comparison with the disease in humans where appropriate. Biology of Vitamin D Activation of Vitamin DVitamin D is available from two sources: isomerization of 7-dehydrocholesterol (7-DHC) in the skin to vitamin D 3 following exposure to ultraviolet light or from ingestion of vitamin D 2 or D 3 in the diet. Only a few foods, including cod liver oil and fatty fish such as salmon and sardines, naturally contain high concentrations of vitamin D 3 .49 Vitamin D 2 i...

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“…1,25(OH) 2 D 3 production in the kidney is regulated positively by many factors, including parathyroid hormone (3) and regulated negatively by others (4), including the phosphate hormone FGF23 (5,6). CYP27B1 is also down-regulated by 1,25(OH) 2 D 3 itself, which exerts strong negative feedback control on CYP27B1 transcription to curb 1,25(OH) 2 D 3 synthesis (3,(7)(8)(9).…”

mentioning

confidence: 99%

A Downstream Intergenic Cluster of Regulatory Enhancers Contributes to the Induction of CYP24A1 Expression by 1α,25-Dihydroxyvitamin D3

Meyer

Goetsch

Pike

2010

Journal of Biological Chemistry

130

120

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The maintenance of active levels of hormone is a dynamic process responsive to a multitude of systemic signals that monitor the mineral status of the organism. 1,25(OH) 2 D 3 production in the kidney is regulated positively by many factors, including parathyroid hormone (3) and regulated negatively by others (4), including the phosphate hormone FGF23 (5, 6). CYP27B1 is also down-regulated by 1,25(OH) 2 D 3 itself, which exerts strong negative feedback control on CYP27B1 transcription to curb 1,25(OH) 2 D 3 synthesis (3, 7-9). Interestingly, this negative feedback mechanism does not appear to be operable in the many extrarenal tissues that are also known to express CYP27B1, albeit at more modest levels (10). 1,25(OH) 2 D 3 also regulates its own degradation as well, because the hormone potently induces CYP24A1 expression in all cells in which it acts (2). Because the magnitude of this induction is generally cell-specific, the regulation of CYP24A1 expression likely represents a mechanism whereby cellular response can be precisely tailored to individual cellular requirements in the face of changing circulating 1,25(OH) 2 D 3 levels. Not surprisingly, reductions in CYP27B1 expression, enhanced synthesis of CYP24A1, or both can lead to a decrease in biologically active 1,25(OH) 2 D 3 levels that results in altered mineral homeostasis and increased disease potential (11). In summary, the collective activity of both renal CYP27B1 and target cell CYP24A1 results in the maintenance of highly dynamic steady-state levels of biologically active 1,25(OH) 2 D 3 in all tissues in which the hormonal ligand is active.The cloning of Cyp24a1 in 1993 revealed Cyp24a1 as a bone fide member of a large family composed of all the cytochrome

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Calcitonin, a Regulator of the 25-Hydroxyvitamin D3 1α-Hydroxylase Gene

Cited by 61 publications

References 58 publications

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

Vitamin D Metabolism and Rickets in Domestic Animals

A Downstream Intergenic Cluster of Regulatory Enhancers Contributes to the Induction of CYP24A1 Expression by 1α,25-Dihydroxyvitamin D3

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