Effect of 24,25-dihydroxyvitamin D3 on 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) metabolism in vitamin D-deficient rats infused with 1,25-(OH)2D3

Journal Article · Sun Jan 01 04:00:00 EST 1989 · Endocrinology; (United States)

DOI:https://doi.org/10.1210/endo-124-1-511· OSTI ID:6540511

Yamato, H; Matsumoto, T; Fukumoto, S; Ikeda, K; Ishizuka, S; Ogata, E

Previous studies revealed that administration of 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3) to calcium (Ca)-deficient rats causes a dose-dependent reduction in markedly elevated serum 1,25-(OH)2D3 level. Although the results suggested that the metabolism of 1,25-(OH)2D3 was accelerated by 24,25-(OH)2D3, those experiments could not define whether the enhanced metabolism of 1,25-(OH)2D3 played a role in the reduction in the serum 1,25-(OH)2D3 level. In the present study, in order to address this issue more specifically, serum 1,25-(OH)2D3 was maintained solely by exogenous administration through miniosmotic pumps of 1,25-(OH)2D3 into vitamin D-deficient rats. Thus, by measuring the serum 1,25-(OH)2D3 concentration, the effect of 24,25-(OH)2D3 on the MCR of 1,25-(OH)2D3 could be examined. Administration of 24,25-(OH)2D3 caused a dose-dependent enhancement in the MCR of 1,25-(OH)2D3, and 1 microgram/100 g rat.day 24,25-(OH)2D3, which elevated serum 24,25-(OH)2D3 to 8.6 +/- 1.3 ng/ml, significantly increased MCR and suppressed serum levels of 1,25-(OH)2D3. The effect of 24,25-(OH)2D3 on 1,25-(OH)2D3 metabolism developed with a rapid time course, and the recovery of iv injected (1 beta-3H)1,25-(OH)2D3 in blood was significantly reduced within 1 h. In addition, there was an increase in radioactivity in the water-soluble fraction of serum as well as in urine, suggesting that 1,25-(OH)2D3 is rapidly degraded to a water-soluble metabolite(s). Furthermore, the reduction in serum 1,25-(OH)2D3 was associated with a reduction in both serum and urinary Ca levels. Because the conversion of (3H)24,25-(OH)2D3 to (3H)1,24,25-(OH)2D3 or other metabolites was minimal in these rats, 24,25-(OH)2D3 appears to act without being converted into other metabolites. These results demonstrate that 24,25-(OH)2D3 rapidly stimulates the metabolism of 1,25-(OH)2D3 and reduces its serum level.

• Research Organization: Univ. of Tokyo School of Medicine (Japan)
• OSTI ID: 6540511
• Journal Information: Endocrinology; (United States), Journal Name: Endocrinology; (United States) Vol. 124:1; ISSN ENDOA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METALS
ANIMALS
CALCIUM
CLEARANCE
DOSE-RESPONSE RELATIONSHIPS
ELEMENTS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
METABOLISM
METABOLITES
METALS
NUTRITIONAL DEFICIENCY
OXYGEN COMPOUNDS
PHOSPHATES
PHOSPHORUS COMPOUNDS
RATS
RODENTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES
VITAMIN D
VITAMINS