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. 1985 Jan;75(1):155–161. doi: 10.1172/JCI111668

Vitamin D status regulates 25-hydroxyvitamin D3-1 alpha-hydroxylase and its responsiveness to parathyroid hormone in the chick.

B E Booth, H C Tsai, R C Morris Jr
PMCID: PMC423421  PMID: 4038405

Abstract

We asked this question: Under normal or near-normal metabolic conditions, does the prevailing normal or near-normal vitamin D status dampen the activity of 25-hydroxyvitamin-D3-1 alpha-hydroxylase (1 alpha-hydroxylase) such that it determines not only its "basal" activity but also its responsiveness to stimulation by increased circulating concentrations of parathyroid hormone (PTH)? To answer this question, we measured the activity of 1 alpha-hydroxylase in chicks, with and without administration of PTH, immediately before and during deprivation of vitamin D. Before deprivation of vitamin D, 1 alpha-hydroxylase activity increased only slightly with administration of PTH. With deprivation of vitamin D for 5 and 10 d, while the plasma concentrations of calcium and phosphorus persisted normal and unchanged, 1 alpha-hydroxylase activity not only increased progressively but also became sharply and increasingly responsive to stimulation by administration of PTH. But after 15 d of vitamin D deprivation, and the supervention of hypocalcemia, 1 alpha-hydroxylase activity was not further increased by the administration of PTH. With deprivation of vitamin D, the progressive increase in 1 alpha-hydroxylase correlated inversely with circulating levels of 1,25-dihydroxyvitamin D (1,25-[OH]2D), and the decreasing calcemic response to PTH correlated inversely with the responsiveness of 1 alpha-hydroxylase to PTH (in chicks deprived of vitamin D for 1-10 d). These results demonstrate that: under normal metabolic conditions, the normal vitamin D status regulates the activity of 1 alpha-hydroxylase so as to dampen both its "basal" activity and its responsiveness to stimulation by PTH; and vitamin D deprivation insufficient to cause hypocalcemia enhances both the "basal" activity of 1 alpha-hydroxylase and its responsiveness to stimulation by PTH. The results suggest that the normal dampening of 1 alpha-hydroxylase and both of the demonstrated enhancements of its activity are mediated by normal and reduced levels of circulating 1,25-(OH)2D, respectively. The finding that PTH fails to further stimulate 1 alpha-hydroxylase when vitamin D deprivation is sufficient in duration to cause hypocalcemia confirms the findings of other investigators and again demonstrates that observations made during abnormal metabolic circumstances may bear little on the physiologic regulation of 1 alpha-hydroxylase under normal or near-normal metabolic circumstances.

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Selected References

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  1. 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]
  2. Baksi S. N., Kenny A. D. Parathyroid hormone stimulation of 1,25-dihydroxyvitamin D3 production in antiestrogen-treated Japanese quail. Mol Pharmacol. 1979 Nov;16(3):932–940. [PubMed] [Google Scholar]
  3. Booth B. E., Tsai H. C., Morris R. C., Jr Parathyroidectomy reduces 25-hydroxyvitamin D3-1 alpha-hydroxylase activity in the hypocalcemic vitamin D-deficient chick. J Clin Invest. 1977 Dec;60(6):1314–1320. doi: 10.1172/JCI108890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Chen T. C., Castillo L., Korycka-Dahl M., DeLuca H. F. Role of vitamin D metabolites in phosphate transport of rat intestine. J Nutr. 1974 Aug;104(8):1056–1060. doi: 10.1093/jn/104.8.1056. [DOI] [PubMed] [Google Scholar]
  6. Colston K. W., Evans I. M., Spelsberg T. C., MacIntyre I. Feedback regulation of vitamin D metabolism by 1,25-dihydroxycholecalciferol. Biochem J. 1977 Apr 15;164(1):83–89. doi: 10.1042/bj1640083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Eisman J. A., Hamstra A. J., Kream B. E., DeLuca H. F. A sensitive, precise, and convenient method for determination of 1,25-dihydroxyvitamin D in human plasma. Arch Biochem Biophys. 1976 Sep;176(1):235–243. doi: 10.1016/0003-9861(76)90161-2. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Fraser D. R. Regulation of the metabolism of vitamin D. Physiol Rev. 1980 Apr;60(2):551–613. doi: 10.1152/physrev.1980.60.2.551. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Garabedian M., Tanaka Y., Holick M. F., Deluca H. F. Response of intestinal calcium transport and bone calcium mobilization to 1,25-dihydroxyvitamin D3 in thyroparathyroidectomized rats. Endocrinology. 1974 Apr;94(4):1022–1027. doi: 10.1210/endo-94-4-1022. [DOI] [PubMed] [Google Scholar]
  13. Garabédian M., Vainsel M., Mallet E., Guillozo H., Toppet M., Grimberg R., NGuyen T. M., Balsan S. Circulating vitamin D metabolite concentrations in children with nutritional rickets. J Pediatr. 1983 Sep;103(3):381–386. doi: 10.1016/s0022-3476(83)80407-7. [DOI] [PubMed] [Google Scholar]
  14. Gonnerman W. A., Ramp W. K., Toverud S. U. Vitamin D, dietary calcium and parathyroid hormone interactions in chicks. Endocrinology. 1975 Feb;96(2):275–281. doi: 10.1210/endo-96-2-275. [DOI] [PubMed] [Google Scholar]
  15. Gray R. W., Napoli J. L. Dietary phosphate deprivation increases 1,25-dihyroxyvitamin D3 synthesis in rat kidney in vitro. J Biol Chem. 1983 Jan 25;258(2):1152–1155. [PubMed] [Google Scholar]
  16. 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]
  17. Harrison J. E., Hitchman A. J., Jones G., Tam C. S., Heersche J. N. Plasma vitamin D metabolite levels in phosphorus deficient rats during the development of vitamin D deficient rickets. Metabolism. 1982 Nov;31(11):1121–1127. doi: 10.1016/0026-0495(82)90162-7. [DOI] [PubMed] [Google Scholar]
  18. Haussler M. R., Baylink D. J., Hughes M. R., Brumbaugh P. F., Wergedal J. E., Shen F. H., Nielsen R. L., Counts S. J., Bursac K. M., McCain T. A. The assay of 1alpha,25-dihydroxyvitamin D3: physiologic and pathologic modulation of circulating hormone levels. Clin Endocrinol (Oxf) 1976;5 (Suppl):151S–165S. doi: 10.1111/j.1365-2265.1976.tb03823.x. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Henry H. L. Regulation of the hydroxylation of 25-hydroxyvitamin D3 in vivo and in primary cultures of chick kidney cells. J Biol Chem. 1979 Apr 25;254(8):2722–2729. [PubMed] [Google Scholar]
  21. Horiuchi N., Suda T., Sasaki S., Takahashi H., Shimazawa E., Ogata E. Absence of regulatory effects of 1alpha25-dihydroxyvitamin D3 on 25-hydroxyvitamin D metabolism in rats constantly infused with parathyroid hormone. Biochem Biophys Res Commun. 1976 Dec 20;73(4):869–875. doi: 10.1016/0006-291x(76)90202-3. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Jones G., DeLuca H. F. High-pressure liquid chromatography: separation of the metabolites of vitamins D2 and D3 on small-particle silica columns. J Lipid Res. 1975 Nov;16(6):448–453. [PubMed] [Google Scholar]
  24. Jowsey J. Calcium release from the skeletons of rachitic puppies. J Clin Invest. 1972 Jan;51(1):9–15. doi: 10.1172/JCI106802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kawashima H., Kurokawa K. Unique hormonal regulation of vitamin D metabolism in the mammalian kidney. Miner Electrolyte Metab. 1983;9(4-6):227–235. [PubMed] [Google Scholar]
  26. Lester G. E., VanderWiel C. J., Gray T. K., Talmage R. V. Vitamin D deficiency in rats with normal serum calcium concentrations. Proc Natl Acad Sci U S A. 1982 Aug;79(15):4791–4794. doi: 10.1073/pnas.79.15.4791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mahoney C. A., Nissenson R. A. Canine renal receptors for parathyroid hormone. Down-regulation in vivo by exogenous parathyroid hormone. J Clin Invest. 1983 Aug;72(2):411–421. doi: 10.1172/JCI110989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mallet E., Nguyen T., Garabedian M., Bassuyau J. P. Circulating parathyroid hormone and dihydroxylated vitamin D metabolites after oral 25 hydroxycholecalciferol in infantile rickets. Horm Metab Res. 1982 Sep;14(9):503–504. doi: 10.1055/s-2007-1019061. [DOI] [PubMed] [Google Scholar]
  29. Mallon J. P., Boris A., Bryce G. F. Decrease in serum levels of 1,25-dihydroxycholecalciferol in rats and chickens fed a vitamin D-deficient diet. J Nutr. 1981 Apr;111(4):665–667. doi: 10.1093/jn/111.4.665. [DOI] [PubMed] [Google Scholar]
  30. Massry S. G., Stein R., Garty J., Arieff A. I., Coburn J. W., Norman A. W., Friedler R. M. Skeletal resistance to the calcemic action of parathyroid hormone in uremia: role of 1,25 (OH)2 D3. Kidney Int. 1976 Jun;9(6):467–474. doi: 10.1038/ki.1976.60. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Norman A. W., Miller B. E., Putkey J. A. Evaluation of the diurnal production of 1,25-dihydroxyvitamin D and vitamin D's effects on intestinal membrane organization. Prog Biochem Pharmacol. 1980;17:160–167. [PubMed] [Google Scholar]
  33. 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]
  34. Omdahl J. L. Interaction of the parathyroid and 1,25-dihydroxyvitamin D3 in the control of renal 25-hydroxyvitamin D3 metabolism. J Biol Chem. 1978 Dec 10;253(23):8474–8478. [PubMed] [Google Scholar]
  35. Papapoulos S. E., Clemens T. L., Fraher L. J., Gleed J., O'Riordan J. L. Metabolites of vitamin D in human vitamin-D deficiency: effect of vitamin D3 or 1,25-dihydroxycholecalciferol. Lancet. 1980 Sep 20;2(8195 Pt 1):612–615. doi: 10.1016/s0140-6736(80)90283-4. [DOI] [PubMed] [Google Scholar]
  36. Shepard R. M., Horst R. L., Hamstra A. J., DeLuca H. F. Determination of vitamin D and its metabolites in plasma from normal and anephric man. Biochem J. 1979 Jul 15;182(1):55–69. doi: 10.1042/bj1820055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Stanbury S. W., Lumb G. A. Parathyroid function in chronic vitamin D deficiency in man: a model for comparison with chronic renal failure. Calcif Tissue Res. 1976 Aug;21 (Suppl):185–201. [PubMed] [Google Scholar]
  38. Stanbury S. W. Vitamin D and hyperparathyroidism: the Lumleian Lecture 1981. J R Coll Physicians Lond. 1981 Oct;15(4):205-9, 212-7. [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. Tanaka Y., DeLuca H. F. Stimulation of 1,25-dihydroxyvitamin D3 production by 1,25-dihydroxyvitamin D3 in the hypocalcaemic rat. Biochem J. 1983 Sep 15;214(3):893–897. doi: 10.1042/bj2140893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Trechsel U., Eisman J. A., Fischer J. A., Bonjour J. P., Fleisch H. Calcium-dependent, parathyroid hormone-independent regulation of 1,25-dihydroxyvitamin D. Am J Physiol. 1980 Aug;239(2):E119–E124. doi: 10.1152/ajpendo.1980.239.2.E119. [DOI] [PubMed] [Google Scholar]
  42. Viansel M., Manderlier T., Corvilain J., Vis H. L. Study of the secondary hyperparathyroidism in vitamin D deficiency rickets. I. Aspects of mineral metabolism. Biomedicine. 1974 Sep 20;21(9):368–371. [PubMed] [Google Scholar]

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