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Temporal changes in tissue 1α,25-dihydroxyvitamin D3, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)2D3 treatment in mice.
Am J Physiol Endocrinol Metab 2013; 304(9):E977-89AJ

Abstract

The vitamin D receptor (VDR) maintains a balance of plasma calcium and 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], its natural active ligand, by directly regulating the calcium ion channel (TRPV6) and degradation enzyme (CYP24A1), and indirectly regulating the parathyroid hormone (PTH) for feedback regulation of the synthetic enzyme CYP27B1. Studies that examined the intricate relationships between plasma and tissue 1,25(OH)2D3 levels and changes in VDR target genes and plasma calcium and PTH are virtually nonexistent. In this study, we investigated temporal correlations between tissue 1,25(OH)2D3 concentrations and VDR target genes in ileum and kidney and plasma calcium and PTH concentrations in response to 1,25(OH)2D3 treatment in mice (2.5 μg/kg ip, singly or q2d × 4). After a single ip dose, plasma 1,25(OH)2D3 peaked at ∼0.5 h and then decayed biexponentially, falling below basal levels after 24 h and then returning to baseline after 8 days. Upon repetitive ip dosing, plasma, ileal, renal, and bone 1,25(OH)2D3 concentrations rose and decayed in unison. Temporal profiles showed increased expressions of ileal Cyp24a1 and renal Cyp24a1, Mdr1/P-gp, and VDR but decreased renal Cyp27b1 mRNA after a time delay in VDR activation. Increased plasma calcium and attenuated PTH levels and increased ileal and renal Trpv6 expression paralleled the changes in tissue 1,25(OH)2D3 concentrations. Gene changes in the kidney were more sustained than those in intestine, but the magnitudes of change for Cyp24a1 and Trpv6 were lower than those in intestine. The data revealed that 1,25(OH)2D3 equilibrates with tissues rapidly, and VDR target genes respond quickly to exogenously administered 1,25(OH)2D3.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23482451

Citation

Chow, Edwin C Y., et al. "Temporal Changes in Tissue 1α,25-dihydroxyvitamin D3, Vitamin D Receptor Target Genes, and Calcium and PTH Levels After 1,25(OH)2D3 Treatment in Mice." American Journal of Physiology. Endocrinology and Metabolism, vol. 304, no. 9, 2013, pp. E977-89.
Chow EC, Quach HP, Vieth R, et al. Temporal changes in tissue 1α,25-dihydroxyvitamin D3, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)2D3 treatment in mice. Am J Physiol Endocrinol Metab. 2013;304(9):E977-89.
Chow, E. C., Quach, H. P., Vieth, R., & Pang, K. S. (2013). Temporal changes in tissue 1α,25-dihydroxyvitamin D3, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)2D3 treatment in mice. American Journal of Physiology. Endocrinology and Metabolism, 304(9), pp. E977-89. doi:10.1152/ajpendo.00489.2012.
Chow EC, et al. Temporal Changes in Tissue 1α,25-dihydroxyvitamin D3, Vitamin D Receptor Target Genes, and Calcium and PTH Levels After 1,25(OH)2D3 Treatment in Mice. Am J Physiol Endocrinol Metab. 2013 May 1;304(9):E977-89. PubMed PMID: 23482451.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Temporal changes in tissue 1α,25-dihydroxyvitamin D3, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)2D3 treatment in mice. AU - Chow,Edwin C Y, AU - Quach,Holly P, AU - Vieth,Reinhold, AU - Pang,K Sandy, Y1 - 2013/03/12/ PY - 2013/3/14/entrez PY - 2013/3/14/pubmed PY - 2013/8/27/medline KW - 1α,25-dihydroxyvitamin D3 KW - 1α-hydroxylase KW - 24-hydroxylase cytochrome P-450 KW - 25-hydroxyvitamin D3 KW - Cyp24a1 KW - Cyp27b1 KW - TRPV6 KW - member 6 KW - subfamily V KW - transient receptor potential cation channel KW - vitamin D receptor SP - E977 EP - 89 JF - American journal of physiology. Endocrinology and metabolism JO - Am. J. Physiol. Endocrinol. Metab. VL - 304 IS - 9 N2 - The vitamin D receptor (VDR) maintains a balance of plasma calcium and 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], its natural active ligand, by directly regulating the calcium ion channel (TRPV6) and degradation enzyme (CYP24A1), and indirectly regulating the parathyroid hormone (PTH) for feedback regulation of the synthetic enzyme CYP27B1. Studies that examined the intricate relationships between plasma and tissue 1,25(OH)2D3 levels and changes in VDR target genes and plasma calcium and PTH are virtually nonexistent. In this study, we investigated temporal correlations between tissue 1,25(OH)2D3 concentrations and VDR target genes in ileum and kidney and plasma calcium and PTH concentrations in response to 1,25(OH)2D3 treatment in mice (2.5 μg/kg ip, singly or q2d × 4). After a single ip dose, plasma 1,25(OH)2D3 peaked at ∼0.5 h and then decayed biexponentially, falling below basal levels after 24 h and then returning to baseline after 8 days. Upon repetitive ip dosing, plasma, ileal, renal, and bone 1,25(OH)2D3 concentrations rose and decayed in unison. Temporal profiles showed increased expressions of ileal Cyp24a1 and renal Cyp24a1, Mdr1/P-gp, and VDR but decreased renal Cyp27b1 mRNA after a time delay in VDR activation. Increased plasma calcium and attenuated PTH levels and increased ileal and renal Trpv6 expression paralleled the changes in tissue 1,25(OH)2D3 concentrations. Gene changes in the kidney were more sustained than those in intestine, but the magnitudes of change for Cyp24a1 and Trpv6 were lower than those in intestine. The data revealed that 1,25(OH)2D3 equilibrates with tissues rapidly, and VDR target genes respond quickly to exogenously administered 1,25(OH)2D3. SN - 1522-1555 UR - https://www.unboundmedicine.com/medline/citation/23482451/Temporal_changes_in_tissue_1α25_dihydroxyvitamin_D3_vitamin_D_receptor_target_genes_and_calcium_and_PTH_levels_after_125_OH_2D3_treatment_in_mice_ L2 - http://www.physiology.org/doi/full/10.1152/ajpendo.00489.2012?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -