24R,25-dihydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3 are both indispensable for calcium and phosphorus homeostasis

Anthony W. Norman; Helen L. Henry; Hartmut H. Malluche

doi:10.1016/0024-3205(80)90142-3

24R,25-dihydroxyvitamin D₃ and 1α,25-dihydroxyvitamin D₃ are both indispensable for calcium and phosphorus homeostasis

Anthony W. Norman, Helen L. Henry, Hartmut H. Malluche

Internal Medicine

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

Abstract

The essential role of vitamin D throughout the life of most mammals and birds as a mediator of calcium homeostasis is well established. In view of the complex endocrine system existent for the regulated metabolism of vitamin D₃ to both 1α,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] and 24R,25-dihydroxyvitamin D₃ [24R,25-(OH)₂D₃] (both produced by the kidney), an intriguing problem is to elucidate whether only one or both of these dihydroxyvitamin D₃ metabolites is required for the generation of all the biological responses mediated by the parent vitamin D₃. In contrast to the accumulated knowledge concerning the short term actions of 1,25(OH)₂-D₃ on stimulating intestinal calcium absorption and bone calcium reabsorption, relatively little is known of the biological function of 24,25(OH)₂D₃. We report now the results of a nine month study in which chicks were raised on a vitamin D-deficient diet from hatching to sexual maturity and received as their sole source of “vitamin D” either 24,25(OH)₂D₃ or 1,25(OH)₂D₃ singly or in combination. Specifically we are describing the integrated operation of the vitamin D endocrine system as quantitated by the individual measurement in all birds of 22 variables related to “vitamin D status” and as evaluated by the statistical procedure of multivariate discriminant analysis. Twelve of these variables involved detailed analysis of the bone including quantitative histology and the other 10 variables reflect various manifestations of vitamin D action, e.g. serum Ca²⁺ and Pi levels, vitamin D-dependent calcium binding protein (CaBP) in the intestine and kidney, egg productivity etc. As evaluated by the multivariate analysis, it is clear that 24,25(OH)₂D₃ and 1,25(OH)₂D₃ are simultaneously required for normalization of calcium homeostasis.

Original language	English
Pages (from-to)	229-237
Number of pages	9
Journal	Life Sciences
Volume	27
Issue number	3
DOIs	https://doi.org/10.1016/0024-3205(80)90142-3
State	Published - 1980

Bibliographical note

Funding Information:
We gratefully acknowledge the dedicated assistance of Mr. B. Thuman, Mr. R. Ochoa, and Ms. J. E. Bishop in rearing and dosing the birds employed over the 9 months of this experiment. Ms. S. Barragan provided skillful technical assistance in the processing and sectioning of the bone samples. Special thanks are due to Mr. C. K. Huszar, Statistics Department, University of California, Riverside for his careful introduction to multivariate analysis. This work was supported in part by USPHS grant (to AWN) AM-09012-014, a grant-in-aid from Hoffmann La Roche, Nutley NJ (to AWN), the Kidney Foundation of Southern California (HHM), and NSF grant PCM 76-24446 (to HLH).

ASJC Scopus subject areas

General Pharmacology, Toxicology and Pharmaceutics
General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/0024-3205(80)90142-3

Cite this

@article{02ea2c2274244f6fa9ee8484530297f8,

title = "24R,25-dihydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3 are both indispensable for calcium and phosphorus homeostasis",

abstract = "The essential role of vitamin D throughout the life of most mammals and birds as a mediator of calcium homeostasis is well established. In view of the complex endocrine system existent for the regulated metabolism of vitamin D3 to both 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] and 24R,25-dihydroxyvitamin D3 [24R,25-(OH)2D3] (both produced by the kidney), an intriguing problem is to elucidate whether only one or both of these dihydroxyvitamin D3 metabolites is required for the generation of all the biological responses mediated by the parent vitamin D3. In contrast to the accumulated knowledge concerning the short term actions of 1,25(OH)2-D3 on stimulating intestinal calcium absorption and bone calcium reabsorption, relatively little is known of the biological function of 24,25(OH)2D3. We report now the results of a nine month study in which chicks were raised on a vitamin D-deficient diet from hatching to sexual maturity and received as their sole source of “vitamin D” either 24,25(OH)2D3 or 1,25(OH)2D3 singly or in combination. Specifically we are describing the integrated operation of the vitamin D endocrine system as quantitated by the individual measurement in all birds of 22 variables related to “vitamin D status” and as evaluated by the statistical procedure of multivariate discriminant analysis. Twelve of these variables involved detailed analysis of the bone including quantitative histology and the other 10 variables reflect various manifestations of vitamin D action, e.g. serum Ca2+ and Pi levels, vitamin D-dependent calcium binding protein (CaBP) in the intestine and kidney, egg productivity etc. As evaluated by the multivariate analysis, it is clear that 24,25(OH)2D3 and 1,25(OH)2D3 are simultaneously required for normalization of calcium homeostasis.",

author = "Norman, {Anthony W.} and Henry, {Helen L.} and Malluche, {Hartmut H.}",

note = "Funding Information: We gratefully acknowledge the dedicated assistance of Mr. B. Thuman, Mr. R. Ochoa, and Ms. J. E. Bishop in rearing and dosing the birds employed over the 9 months of this experiment. Ms. S. Barragan provided skillful technical assistance in the processing and sectioning of the bone samples. Special thanks are due to Mr. C. K. Huszar, Statistics Department, University of California, Riverside for his careful introduction to multivariate analysis. This work was supported in part by USPHS grant (to AWN) AM-09012-014, a grant-in-aid from Hoffmann La Roche, Nutley NJ (to AWN), the Kidney Foundation of Southern California (HHM), and NSF grant PCM 76-24446 (to HLH).",

year = "1980",

doi = "10.1016/0024-3205(80)90142-3",

language = "English",

volume = "27",

pages = "229--237",

number = "3",

}

TY - JOUR

T1 - 24R,25-dihydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3 are both indispensable for calcium and phosphorus homeostasis

AU - Norman, Anthony W.

AU - Henry, Helen L.

AU - Malluche, Hartmut H.

N1 - Funding Information: We gratefully acknowledge the dedicated assistance of Mr. B. Thuman, Mr. R. Ochoa, and Ms. J. E. Bishop in rearing and dosing the birds employed over the 9 months of this experiment. Ms. S. Barragan provided skillful technical assistance in the processing and sectioning of the bone samples. Special thanks are due to Mr. C. K. Huszar, Statistics Department, University of California, Riverside for his careful introduction to multivariate analysis. This work was supported in part by USPHS grant (to AWN) AM-09012-014, a grant-in-aid from Hoffmann La Roche, Nutley NJ (to AWN), the Kidney Foundation of Southern California (HHM), and NSF grant PCM 76-24446 (to HLH).

PY - 1980

Y1 - 1980

N2 - The essential role of vitamin D throughout the life of most mammals and birds as a mediator of calcium homeostasis is well established. In view of the complex endocrine system existent for the regulated metabolism of vitamin D3 to both 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] and 24R,25-dihydroxyvitamin D3 [24R,25-(OH)2D3] (both produced by the kidney), an intriguing problem is to elucidate whether only one or both of these dihydroxyvitamin D3 metabolites is required for the generation of all the biological responses mediated by the parent vitamin D3. In contrast to the accumulated knowledge concerning the short term actions of 1,25(OH)2-D3 on stimulating intestinal calcium absorption and bone calcium reabsorption, relatively little is known of the biological function of 24,25(OH)2D3. We report now the results of a nine month study in which chicks were raised on a vitamin D-deficient diet from hatching to sexual maturity and received as their sole source of “vitamin D” either 24,25(OH)2D3 or 1,25(OH)2D3 singly or in combination. Specifically we are describing the integrated operation of the vitamin D endocrine system as quantitated by the individual measurement in all birds of 22 variables related to “vitamin D status” and as evaluated by the statistical procedure of multivariate discriminant analysis. Twelve of these variables involved detailed analysis of the bone including quantitative histology and the other 10 variables reflect various manifestations of vitamin D action, e.g. serum Ca2+ and Pi levels, vitamin D-dependent calcium binding protein (CaBP) in the intestine and kidney, egg productivity etc. As evaluated by the multivariate analysis, it is clear that 24,25(OH)2D3 and 1,25(OH)2D3 are simultaneously required for normalization of calcium homeostasis.

AB - The essential role of vitamin D throughout the life of most mammals and birds as a mediator of calcium homeostasis is well established. In view of the complex endocrine system existent for the regulated metabolism of vitamin D3 to both 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] and 24R,25-dihydroxyvitamin D3 [24R,25-(OH)2D3] (both produced by the kidney), an intriguing problem is to elucidate whether only one or both of these dihydroxyvitamin D3 metabolites is required for the generation of all the biological responses mediated by the parent vitamin D3. In contrast to the accumulated knowledge concerning the short term actions of 1,25(OH)2-D3 on stimulating intestinal calcium absorption and bone calcium reabsorption, relatively little is known of the biological function of 24,25(OH)2D3. We report now the results of a nine month study in which chicks were raised on a vitamin D-deficient diet from hatching to sexual maturity and received as their sole source of “vitamin D” either 24,25(OH)2D3 or 1,25(OH)2D3 singly or in combination. Specifically we are describing the integrated operation of the vitamin D endocrine system as quantitated by the individual measurement in all birds of 22 variables related to “vitamin D status” and as evaluated by the statistical procedure of multivariate discriminant analysis. Twelve of these variables involved detailed analysis of the bone including quantitative histology and the other 10 variables reflect various manifestations of vitamin D action, e.g. serum Ca2+ and Pi levels, vitamin D-dependent calcium binding protein (CaBP) in the intestine and kidney, egg productivity etc. As evaluated by the multivariate analysis, it is clear that 24,25(OH)2D3 and 1,25(OH)2D3 are simultaneously required for normalization of calcium homeostasis.

UR - http://www.scopus.com/inward/record.url?scp=0019195340&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0019195340&partnerID=8YFLogxK

U2 - 10.1016/0024-3205(80)90142-3

DO - 10.1016/0024-3205(80)90142-3

M3 - Article

C2 - 6967551

AN - SCOPUS:0019195340

SN - 0024-3205

VL - 27

SP - 229

EP - 237

JO - Life Sciences

JF - Life Sciences

IS - 3

ER -