Chronic 1,25-dihydroxyvitamin D3 administration in the rat reduces the serum concentration of 25-hydroxyvitamin D by increasing metabolic clearance rate

• Published in: The Journal of clinical investigation Vol. 78; no. 3; pp. 622 - 628
• Main Authors: HALLORAN, B. P, BIKLE, D. D, LEVENS, M. J, CASTRO, M. E, GLOBUS, R. K, HOLTON, E
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01.09.1986
• Subjects: 24,25-Dihydroxyvitamin D 3; Animals; Biological and medical sciences; Calcifediol - blood; Calcifediol - metabolism; Calcitriol - administration & dosage; Calcitriol - pharmacology; Calcium - administration & dosage; Calcium - blood; Dihydroxycholecalciferols - blood; Dihydroxycholecalciferols - metabolism; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Kidney - drug effects; Kidney - metabolism; Liver - drug effects; Liver - metabolism; Male; Metabolic Clearance Rate; Rats; Rats, Inbred Strains; Space life sciences; Steroid hormones. Cholecalciferol derivatives; Vertebrates: endocrinology; Cholecalciferol(hydroxy-25); Route of administration; Steroid hormone; Cholecalciferol(dihydroxy-1,25); Blood
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI112619

Administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] can lower the serum concentration of 25-hydroxyvitamin (25-OH-D). To determine if 1,25(OH)2D3 lowers serum 25-OH-D by increasing clearance or reducing production, we directly measured the metabolic clearance rate (MCR) of 25-OH-D in rats chronically infused with 1,25(OH)2D3. Chronic 1,25(OH)2D3 administration (0 to 75 pmol/d) reduced, in a time- and dose-dependent fashion, the serum concentrations of 25-OH-D3 and 24,25(OH)2D3 from 18 +/- 2 to 9 +/- 1 ng/ml and from 4.8 +/- 0.7 to 1.3 +/- 0.3 ng/ml, respectively, and increased sevenfold the in vitro conversion of 25-OH-D to 24,25(OH)2D3 by kidney homogenates. The reduction in serum 25-OH-D3 was completely accounted for by an increase in MCR. No change in production occurred. The influence of 1,25(OH)2D3 on serum 25-OH-D3 and 24,25(OH)2D3 was shown not to be dependent on induction of hypercalcemia. These data suggest that chronic 1,25(OH)2D3 administration lowers serum 25-OH-D by increasing the metabolic clearance of 25-OH-D3 and not by decreasing its production.