Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1980 Oct;66(4):664–669. doi: 10.1172/JCI109902

Production, degradation, and circulating levels of 1,25-dihydroxyvitamin D in health and in chronic glucocorticoid excess.

E Seeman, R Kumar, G G Hunder, M Scott, H Heath 3rd, B L Riggs
PMCID: PMC371639  PMID: 7419714

Abstract

The decreased intestinal absorption of calcium and accelerated bone loss associated with chronic glucocorticoid excess may be mediated by changes in vitamin D metabolism, leading to decreased availability of circulating 1,25-dihydroxyvitamin D. This hypothesis was examined in 14 patients with either endogenous or exogenous glucocorticoid excess. Analysis of paired serum samples (mean +/- SE) in 13 patients during euglucocorticoidism and during hyperglucocorticoidism showed that glucocorticoid excess resulted in small decreases of plasma 25-hydroxy-vitamin D concentrations (22 +/- 2- 18 +/- 2 ng/ml; P < 0.05) but no significant changes in plasma 1,25-dihydroxyvitamin D (32 +/- 8- 23 +/- 6 pg/ml) or serum immunoreactive parathyroid hormone (21 +/- 2- 18 +/- 2 muleq/ml). Additionally, we studied plasma kinetics of [3H]1,25-dihydroxyvitamin D3 after intravenous bolus administration in 10 hyperglucocorticoid patients and in 14 normal controls. Assessment with a three-compartment model showed no significant abnormalities in production rates (hyperglucocorticoid patients 1.2 +/- 0.3 micrograms/d, controls 1.5 +/- 0.2 micrograms/d) or metabolic clearance rates (hyperglucocorticoid patients, 18 +/- 2%; controls, 14 +/- 2%) or feces (hyperglucocorticoid patients, 60 +/- 9%, controls, 54 +/- 6%). We conclude that glucocorticoid excess does not effect plasma levels, production, or degradation of 1,25(OH)2D in humans. Thus, other mechanisms must be postulated to explain satisfactorily the abnormalities of bone structure and intestinal calcium absorption that may occur after chronic glucocorticoid therapy.

Full text

PDF
668

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnaud C. D., Goldsmith R. S., Bordier P. J., Sizemore G. W. Influence of immunoheterogeneity of circulating parathyroid hormone on results of radioimmunoassays of serum in man. Am J Med. 1974 Jun;56(6):785–793. doi: 10.1016/0002-9343(74)90806-7. [DOI] [PubMed] [Google Scholar]
  2. Arnaud C. D., Tsao H. S., Littledike T. Radioimmunoassay of human parathyroid hormone in serum. J Clin Invest. 1971 Jan;50(1):21–34. doi: 10.1172/JCI106476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Avioli L. V., Birge S. J., Lee S. W. Effects of prednisone on vitamin D metabolism in man. J Clin Endocrinol Metab. 1968 Sep;28(9):1341–1346. doi: 10.1210/jcem-28-9-1341. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. De Luca H. F. Recent advances in our understanding of the vitamin D endocrine system. J Lab Clin Med. 1976 Jan;87(1):7–26. [PubMed] [Google Scholar]
  6. 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]
  7. Favus M. J., Kimberg D. V., Millar G. N., Gershon E. Effects of cortisone administration on the metabolism and localization of 25-hydroxycholecalciferol in the rat. J Clin Invest. 1973 Jun;52(6):1328–1335. doi: 10.1172/JCI107304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fucik R. F., Kukreja S. C., Hargis G. K., Bowser E. N., Henderson W. J., Williams G. A. Effect of glucocorticoids on function of the parathyroid glands in man. J Clin Endocrinol Metab. 1975 Jan;40(1):152–155. doi: 10.1210/jcem-40-1-152. [DOI] [PubMed] [Google Scholar]
  9. Gallagher J. C., Riggs B. L., Jerpbak C. M., Arnaud C. D. The effect of age on serum immunoreactive parathyroid hormone in normal and osteoporotic women. J Lab Clin Med. 1980 Mar;95(3):373–385. [PubMed] [Google Scholar]
  10. Gray R. W., Caldas A. E., Wilz D. R., Lemann J., Jr, Smith G. A., DeLuca H. F. Metabolism and excretion of 3H-1,25-(OH)2-vitamin D3 in healthy adults. J Clin Endocrinol Metab. 1978 May;46(5):756–765. doi: 10.1210/jcem-46-5-756. [DOI] [PubMed] [Google Scholar]
  11. Gray R. W., Omdahl J. L., Ghazarian J. G., DeLuca H. F. 25-Hydroxycholecalciferol-1-hydroxylase. Subcellular location and properties. J Biol Chem. 1972 Dec 10;247(23):7528–7532. [PubMed] [Google Scholar]
  12. HARRISON H. E., HARRISON H. C. Transfer of Ca45 across intestinal wall in vitro in relation to action of vitamin D and cortisol. Am J Physiol. 1960 Aug;199:265–271. doi: 10.1152/ajplegacy.1960.199.2.265. [DOI] [PubMed] [Google Scholar]
  13. Haddad J. G., Chyu K. J. Competitive protein-binding radioassay for 25-hydroxycholecalciferol. J Clin Endocrinol Metab. 1971 Dec;33(6):992–995. doi: 10.1210/jcem-33-6-992. [DOI] [PubMed] [Google Scholar]
  14. Kimberg D. V. Effects of vitamin D and steroid hormones on the active transport of calcium by the intestine. N Engl J Med. 1969 Jun 19;280(25):1396–1405. doi: 10.1056/NEJM196906192802510. [DOI] [PubMed] [Google Scholar]
  15. Klein R. G., Arnaud S. B., Gallagher J. C., Deluca H. F., Riggs B. L. Intestinal calcium absorption in exogenous hypercortisonism. Role of 25-hydroxyvitamin D and corticosteroid dose. J Clin Invest. 1977 Jul;60(1):253–259. doi: 10.1172/JCI108762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kooh S. W., Fraser D., DeLuca H. F., Holick M. F., Belsey R. E., Clark M. B., Murray T. M. Treatment of hypoparathyroidism and pseudohypoparathyroidism with metabolites of vitamin D: evidence for impaired conversion of 25-hydroxyvitamin D to 1 alpha,25-dihydroxyvitamin D. N Engl J Med. 1975 Oct 23;293(17):840–844. doi: 10.1056/NEJM197510232931702. [DOI] [PubMed] [Google Scholar]
  17. Kumar R., Cohen W. R., Silva P., Epstein F. H. Elevated 1,25-dihydroxyvitamin D plasma levels in normal human pregnancy and lactation. J Clin Invest. 1979 Feb;63(2):342–344. doi: 10.1172/JCI109308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kumar R., Nagubandi S., Mattox V. R., Londowski J. M. Enterohepatic physiology of 1,25-dihydroxyvitamin D3. J Clin Invest. 1980 Feb;65(2):277–284. doi: 10.1172/JCI109669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mawer E. B., Backhouse J., Davies M., Hill L. F., Taylor C. M. Metabolic fate of administered 1,25-dihydroxycholecalciferol in controls and in patients with hypoparathyroidism. Lancet. 1976 Jun 5;1(7971):1203–1206. doi: 10.1016/s0140-6736(76)92157-7. [DOI] [PubMed] [Google Scholar]
  20. WILLIAMS G. A., BOWSER E. N., HENDERSON W. J., UZGIRIES V. Effects of vitamin D and cortisone on intestinal absorption of calcium in the rat. Proc Soc Exp Biol Med. 1961 Mar;106:664–666. doi: 10.3181/00379727-106-26436. [DOI] [PubMed] [Google Scholar]
  21. Wajchenberg B. L., Pereira V. G., Kieffer J., Ursic S. Effect of dexamethasone on calcium metabolism and 47Ca kinetics in normal subjects. Acta Endocrinol (Copenh) 1969 May;61(1):173–192. doi: 10.1530/acta.0.0610173. [DOI] [PubMed] [Google Scholar]
  22. Wilkinson R. Polyethylene glycol 4000 as a continuously administered non-absorbable faecal marker for metabolic balance studies in human subjects. Gut. 1971 Aug;12(8):654–660. doi: 10.1136/gut.12.8.654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Williams G. A., Peterson W. C., Bowser E. N., Henderson W. J., Hargis G. K., Martinez N. J. Interrelationship of parathyroid and adrenocortical function in calcium homeostasis in the rat. Endocrinology. 1974 Sep;95(3):707–712. doi: 10.1210/endo-95-3-707. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES