Abstract
To test the hypothesis that in the vitamin D-deficient state the activity of 25-hydroxyvitamin D3-1 alpha-hydroxylase (25-OHD3-1 alpha-hydroxylase) is modulated by parathyroid hormone and the plasma concentration of phosphate only in the presence of small amounts of 1,25-dihydroxyvitamin D3 (or some other metabolite of vitamin D), we measured the activity of this enzyme 24 h after parathyroidectomy (PTX) in frankly hypocalcemic, vitamin D-deficient chicks that were not supplemented with vitamin D or one of its metabolites. The otherwise predictable complications of PTX in this metabolic setting (hypocalcemia of increasing severity, tetany, moribundity, and death) were prevented by continuous intravenous administration of calcium (as a solution of calcium chloride/calcium gluconate 1:1) through a catheter in the external jugular vein placed at the time of PTX. The findings were as follows: (a) The activity of 25-OHD3-1 alpha-hydroxylase was significantly less in the parathyroidectomized group than in the sham-operated control chicks (P less than 0.001). (b) The reductive effect of PTX on the activity of this enzyme was significantly attenuated when hypophosphatemia was increased in severity by administration of glucose. (c) In the post-PTX state the activity of 25-OHD3-1 alpha-hydroxylase and plasma concentration of phosphate were significantly, inversely related (P less than 0.001). (d) In the sham-operated control group the activity of this enzyme and the plasma concentration of phosphate were not significantly correlated. These findings indicate that in the vitamin D-deficient state, both circulating parathyroid hormone and the plasma concentration of phosphate can significantly modulate the activity of 25-OHD3-1 alpha-hydroxylase in the absence of vitamin D or its metabolites. The findings also suggest that in the vitamin D-deficient state the plasma concentration of phosphate modulates the activity of this enzyme only when the concentration of circulating parathyroid hormone is not increased.
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- BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
- Baxter L. A., DeLuca H. F. Stimulation of 25-hydroxyvitamin D3-1alpha-hydroxylase by phosphate depletion. J Biol Chem. 1976 May 25;251(10):3158–3161. [PubMed] [Google Scholar]
- Boyle I. T., Gray R. W., DeLuca H. F. Regulation by calcium of in vivo synthesis of 1,25-dihydroxycholecalciferol and 21,25-dihydroxycholecalciferol. Proc Natl Acad Sci U S A. 1971 Sep;68(9):2131–2134. doi: 10.1073/pnas.68.9.2131. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boyle I. T., Miravet L., Gray R. W., Holick M. F., Deluca H. F. The response of intestinal calcium transport to 25-hydroxy and 1,25-dihydroxy vitamin D in nephrectomized rats. Endocrinology. 1972 Mar;90(3):605–608. doi: 10.1210/endo-90-3-605. [DOI] [PubMed] [Google Scholar]
- Castillo L., Tanaka Y., DeLuca H. F. The mobilization of bone mineral by 1,25-dihydroxyvitamin D3 in hypophosphatemic rats. Endocrinology. 1975 Oct;97(4):995–999. doi: 10.1210/endo-97-4-995. [DOI] [PubMed] [Google Scholar]
- DeLuca H. F., Schnoes H. K. Metabolism and mechanism of action of vitamin D. Annu Rev Biochem. 1976;45:631–666. doi: 10.1146/annurev.bi.45.070176.003215. [DOI] [PubMed] [Google Scholar]
- Fraser D. R., Kodicek E. Regulation of 25-hydroxycholecalciferol-1-hydroxylase activity in kidney by parathyroid hormone. Nat New Biol. 1973 Feb 7;241(110):163–166. doi: 10.1038/newbio241163a0. [DOI] [PubMed] [Google Scholar]
- Fraser D. R., Kodicek E. Unique biosynthesis by kidney of a biological active vitamin D metabolite. Nature. 1970 Nov 21;228(5273):764–766. doi: 10.1038/228764a0. [DOI] [PubMed] [Google Scholar]
- Galante L., Colston K. W., Evans I. M., Byfield P. G., Matthews E. W., MacIntyre I. The regulation of vitamin D metabolism. Nature. 1973 Aug 17;244(5416):438–440. doi: 10.1038/244438a0. [DOI] [PubMed] [Google Scholar]
- Garabedian M., Holick M. F., Deluca H. F., Boyle I. T. Control of 25-hydroxycholecalciferol metabolism by parathyroid glands. Proc Natl Acad Sci U S A. 1972 Jul;69(7):1673–1676. doi: 10.1073/pnas.69.7.1673. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gray R., Boyle I., DeLuca H. F. Vitamin D metabolism: the role of kidney tissue. Science. 1971 Jun 18;172(3989):1232–1234. doi: 10.1126/science.172.3989.1232. [DOI] [PubMed] [Google Scholar]
- Haussler M. R., Rasmussen H. The metabolism of vitamin D 3 in the chick. J Biol Chem. 1972 Apr 25;247(8):2328–2335. [PubMed] [Google Scholar]
- Henry H. L., Midgett R. J., Norman A. W. Regulation of 25-hydroxyvitamin D3-1-hydroxylase in vivo. J Biol Chem. 1974 Dec 10;249(23):7584–7592. [PubMed] [Google Scholar]
- Holick M. F., DeLuca H. F. A new chromatographic system for vitamin D3 and its metabolites: resoluation of a new vitamin D3 metabolite. J Lipid Res. 1971 Jul;12(4):460–465. [PubMed] [Google Scholar]
- Holick M. F., Garabedian M., DeLuca H. F. 1,25-dihydroxycholecalciferol: metabolite of vitamin D3 active on bone in anephric rats. Science. 1972 Jun 9;176(4039):1146–1147. doi: 10.1126/science.176.4039.1146. [DOI] [PubMed] [Google Scholar]
- Holick M. F., Schnoes H. K., DeLuca H. F., Gray R. W., Boyle I. T., Suda T. Isolation and identification of 24,25-dihydroxycholecalciferol, a metabolite of vitamin D made in the kidney. Biochemistry. 1972 Nov 7;11(23):4251–4255. doi: 10.1021/bi00773a009. [DOI] [PubMed] [Google Scholar]
- Hughes M. R., Baylink D. J., Gonnerman W. A., Toverud S. U., Ramp W. K., Haussler M. R. Influence of dietary vitamin D3 on the circulating concentration of its active metabolites in the chick and rat. Endocrinology. 1977 Mar;100(3):799–806. doi: 10.1210/endo-100-3-799. [DOI] [PubMed] [Google Scholar]
- MacIntyre I., Colston K. W., Evans I. M. The regulation of vitamin D metabolism. Calcif Tissue Res. 1976 Aug;21 (Suppl):136–141. [PubMed] [Google Scholar]
- Mason J. B., Hay R. W., Leresche J., Peel S., Darley S. The story of vitamin D: from vitamin to hormone. Lancet. 1974 Mar 2;1(7853):325–329. [PubMed] [Google Scholar]
- Midgett R. J., Spielvogel A. M., Coburn J. W., Norman A. W. Studies on calciferol metabolism. VII. The renal production of the biologically active form of vitamin D, 1,25-dihydroxycholecalciferol; species, tissue and subcellular distribution. J Clin Endocrinol Metab. 1973 Jun;36(6):1153–1161. doi: 10.1210/jcem-36-6-1153. [DOI] [PubMed] [Google Scholar]
- Norman A. W., Henry H. 1,25-Dihydroxycholecalciferol--a hormonally active form of vitamin D. Recent Prog Horm Res. 1974;30(0):431–480. [PubMed] [Google Scholar]
- Norman A. W., Wong R. G. Biological activity of the vitamin D metabolite 1,25-dihydroxycholecalciferol in chickens and rats. J Nutr. 1972 Dec;102(12):1709–1718. doi: 10.1093/jn/102.12.1709. [DOI] [PubMed] [Google Scholar]
- Rasmussen H., Wong M., Bikle D., Goodman D. B. Hormonal control of the renal conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol. J Clin Invest. 1972 Sep;51(9):2502–2504. doi: 10.1172/JCI107065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tahaka Y., Lorenc R. S., DeLuca H. F. The role of 1,25-dihydroxyvitamin D3 and parathyroid hormone in the regulation of chick renal 25-hydroxyvitamin D3-24-hydroxylase. Arch Biochem Biophys. 1975 Dec;171(2):521–526. doi: 10.1016/0003-9861(75)90061-2. [DOI] [PubMed] [Google Scholar]
- Tanaka Y., DeLuca H. F. Stimulation of 24,25-dihydroxyvitamin D3 production by 1,25-dihydroxyvitamin D3. Science. 1974 Mar;183(130):1198–1200. doi: 10.1126/science.183.4130.1198. [DOI] [PubMed] [Google Scholar]
- Tanaka Y., Deluca H. F. The control of 25-hydroxyvitamin D metabolism by inorganic phosphorus. Arch Biochem Biophys. 1973 Feb;154(2):566–574. doi: 10.1016/0003-9861(73)90010-6. [DOI] [PubMed] [Google Scholar]