Chronic 1,25-dihydroxyvitamin D3 administration in the rat reduces the serum concentration of 25-hydroxyvitamin D by increasing metabolic clearance rate
B P Halloran, D D Bikle, M J Levens, M E Castro, R K Globus, E Holton, B P Halloran, D D Bikle, M J Levens, M E Castro, R K Globus, E Holton
Abstract
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.
References
- J Nutr. 1970 Sep;100(9):1049-52
- J Clin Endocrinol Metab. 1963 Dec;23:1285-97
- J Clin Invest. 1976 Jul;58(1):61-70
- Endocrinology. 1977 Oct;101(4):1184-93
- Calcif Tissue Res. 1977 May;22 Suppl:24-8
- Anal Biochem. 1978 Mar;85(1):86-9
- Biochem J. 1978 Jul 15;174(1):231-6
- J Biol Chem. 1979 Apr 25;254(8):2722-9
- J Clin Invest. 1979 Jul;64(1):206-17
- J Clin Endocrinol Metab. 1979 Aug;49(2):171-5
- Biochem J. 1979 Jul 15;182(1):55-69
- Biochim Biophys Acta. 1979 Nov 1;587(4):495-506
- Physiol Rev. 1980 Apr;60(2):551-613
- J Clin Invest. 1980 Oct;66(4):852-5
- Biochim Biophys Acta. 1980 Sep 9;615(1):208-22
- J Clin Invest. 1981 Jan;67(1):274-80
- J Biol Chem. 1982 Mar 10;257(5):2504-8
- Ann Intern Med. 1982 May;96(5):586-91
- Calcif Tissue Int. 1982;34(6):539-41
- Annu Rev Biochem. 1983;52:411-39
- Calcif Tissue Int. 1983 Jul;35(4-5):461-4
- J Clin Endocrinol Metab. 1984 Jan;58(1):91-8
- J Clin Invest. 1984 Oct;74(4):1540-4
- J Clin Endocrinol Metab. 1984 Dec;59(6):1063-9
- Arch Biochem Biophys. 1985 Nov 1;242(2):488-92
- J Clin Invest. 1962 Dec;41:2093-100
- Am J Med. 1974 Jul;57(1):57-62
Source: PubMed