Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1981 Mar;67(3):589–596. doi: 10.1172/JCI110072

Influence of the Vitamin D-binding Protein on the Serum Concentration of 1,25-Dihydroxyvitamin D3

SIGNIFICANCE OF THE FREE 1,25-DIHYDROXYVITAMIN D3 CONCENTRATION

Roger Bouillon 1, Frans A Van Assche 1, Hugo Van Baelen 1, Walter Heyns 1, Pieter De Moor 1
PMCID: PMC370606  PMID: 6894152

Abstract

The influence of the serum binding protein (DBP) for vitamin D and its metabolites on the concentration of its main ligands, 25-hydroxyvitamin D3 (25-OHD3) and 1,25-dihydroxyvitamin D3 (1,25-[OH]2D3) was studied. The concentration of both 1,25-(OH)2D3 and DBP in normal female subjects (45±14 ng/liter and 333±58 mg/liter, mean±SD, respectively; n = 58) increased during the intake of estro-progestogens (69±27 ng/liter and 488±90 mg/liter, respectively; n = 29), whereas the 25-OHD3 concentration remained unchanged. A positive correlation was found between the concentrations of 1,25-(OH)2D3 and DBP in these women.

At the end of pregnancy, the total concentrations of 1,25-(OH)2D3 (97±26 ng/liter, n = 40) and DBP (616±84 mg/liter) are both significantly higher than in nonpregnant females and paired cord serum samples (48±11 ng/liter and 266±41 mg/liter, respectively). A marked seasonal variation of 25-OHD3 was observed in pregnant females and their infants, whereas in the same samples the concentrations of both DBP and 1,25-(OH)2D3 remained constant throughout the year.

The free 1,25-(OH)2D3 index, calculated as the molar ratio of this steroid and DBP, remains normal in women taking estro-progestogens, however, and this might explain their normal intestinal calcium absorption despite a high total 1,25-(OH)2D3 concentration. In pregnancy the free 1,25-(OH)2D3 index remains normal up to 35 wk of gestation, but during the last weeks of gestation, the free 1,25-(OH)2D3 index increases in both circulations. A highly significant correlation exists between the (total and free) 25-OHD3 and 1,25-(OH)2D3 concentrations in maternal and cord serum both at 35 and 40 wk of gestation.

Full text

PDF
589

Selected References

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

  1. Baksi S. N., Kenny A. D. Vitamim D3 metabolism in immature Japanese quail: effects of ovarian hormones. Endocrinology. 1977 Oct;101(4):1216–1220. doi: 10.1210/endo-101-4-1216. [DOI] [PubMed] [Google Scholar]
  2. Barlet J. P., Davicco M. J., Lefaivre J., Carrillo B. J. Fetal blood calcium response to maternal hypercalcemia induced in the cow by calcium infusion or by solanum glaucophyllum ingestion. Horm Metab Res. 1979 Jan;11(1):57–60. [PubMed] [Google Scholar]
  3. Baumann G., Rappaport G., Lemarchand-Béraud T., Felber J. P. Free cortisol index: a rapid and simple estimation of free cortisol in human plasma. J Clin Endocrinol Metab. 1975 Mar;40(3):462–469. doi: 10.1210/jcem-40-3-462. [DOI] [PubMed] [Google Scholar]
  4. Bell N. H., Stern P. H., Pantzer E., Sinha T. K., DeLuca H. F. Evidence that increased circulating 1 alpha, 25-dihydroxyvitamin D is the probable cause for abnormal calcium metabolism in sarcoidosis. J Clin Invest. 1979 Jul;64(1):218–225. doi: 10.1172/JCI109442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bouillon R., Kerkhove P. V., De Moor P. Measurement of 25-hydroxyvitamin D3 in serum. Clin Chem. 1976 Mar;22(3):364–368. [PubMed] [Google Scholar]
  6. Bouillon R., Van Baelen H., De Moor P. 25-hydroxyvitamin D and its binding protein in maternal and cord serum. J Clin Endocrinol Metab. 1977 Oct;45(4):679–684. doi: 10.1210/jcem-45-4-679. [DOI] [PubMed] [Google Scholar]
  7. Bouillon R., Van Kerkhove P., De Moor P. Characteristics of the vitamin D binding protein in different species. Calcif Tissue Res. 1976 Aug;21 (Suppl):172–176. [PubMed] [Google Scholar]
  8. Bouillon R., Vandoren G., Van Baelen H., De Moor P. Immunochemical measurement of the vitamin D-binding protein in rat serum. Endocrinology. 1978 Jun;102(6):1710–1715. doi: 10.1210/endo-102-6-1710. [DOI] [PubMed] [Google Scholar]
  9. Bouillon R., de Moor P. Pathophysiological data obtained with a radioimmunoassay for human parathyroid hormone. Ann Endocrinol (Paris) 1973 Nov-Dec;34(6):657–668. [PubMed] [Google Scholar]
  10. Bouillon R., van Baelen H., de Moor P. Comparative study of the affinity of the serum vitamin D-binding protein. J Steroid Biochem. 1980 Sep;13(9):1029–1034. doi: 10.1016/0022-4731(80)90133-8. [DOI] [PubMed] [Google Scholar]
  11. Bouillon R., van Baelen H., de Moor P. The measurement of the vitamin D-binding protein in human serum. J Clin Endocrinol Metab. 1977 Aug;45(2):225–231. doi: 10.1210/jcem-45-2-225. [DOI] [PubMed] [Google Scholar]
  12. Brown D. J., Spanos E., MacIntyre I. Role of pituitary hormones in regulating renal vitamin D metabolism in man. Br Med J. 1980 Feb 2;280(6210):277–278. doi: 10.1136/bmj.280.6210.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cushard W. G., Jr, Creditor M. A., Canterbury J. M., Reiss E. Physiologic hyperparathyroidism in pregnancy. J Clin Endocrinol Metab. 1972 May;34(5):767–771. doi: 10.1210/jcem-34-5-767. [DOI] [PubMed] [Google Scholar]
  14. DE MOOR P., HEIRWEGH K., HEREMANS J. F., DECLERCK-RASKIN M. Protein binding of corticoids studied by gel filtration. J Clin Invest. 1962 Apr;41:816–827. doi: 10.1172/JCI104539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dent C. E., Gupta M. M. Plasma 25-hydroxyvitamin-D-levels during pregnancy in Caucasians and in vegetarian and non-vegetarian Asians. Lancet. 1975 Nov 29;2(7944):1057–1060. doi: 10.1016/s0140-6736(75)90430-4. [DOI] [PubMed] [Google Scholar]
  16. Eskildsen P. C., Lund B., Sørensen O. H., Lund B., Bishop J. E., Norman A. W. Acromegaly and vitamin D metabolism: effect of bromocriptine treatment. J Clin Endocrinol Metab. 1979 Sep;49(3):484–486. doi: 10.1210/jcem-49-3-484. [DOI] [PubMed] [Google Scholar]
  17. Forfar J. O. Normal and abnormal calcium, phosphorus and magnesium metabolism in the perinatal period. Clin Endocrinol Metab. 1976 Mar;5(1):123–148. doi: 10.1016/s0300-595x(76)80011-4. [DOI] [PubMed] [Google Scholar]
  18. Gallagher J. C., Aaron J., Horsman A., Marshall D. H., Wilkinson R., Nordin B. E. The crush fracture syndrome in postmenopausal women. Clin Endocrinol Metab. 1973 Jul;2(2):293–315. doi: 10.1016/s0300-595x(73)80045-3. [DOI] [PubMed] [Google Scholar]
  19. Gallagher J. C., Riggs B. L., Eisman J., Hamstra A., Arnaud S. B., DeLuca H. F. Intestinal calcium absorption and serum vitamin D metabolites in normal subjects and osteoporotic patients: effect of age and dietary calcium. J Clin Invest. 1979 Sep;64(3):729–736. doi: 10.1172/JCI109516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gray R. W., Wilz D. R., Caldas A. E., Lemann J., Jr The importance of phosphate in regulating plasma 1,25-(OH)2-vitamin D levels in humans: studies in healthy subjects in calcium-stone formers and in patients with primary hyperparathyroidism. J Clin Endocrinol Metab. 1977 Aug;45(2):299–306. doi: 10.1210/jcem-45-2-299. [DOI] [PubMed] [Google Scholar]
  21. Gray T. K., Lester G. E., Lorenc R. S. Evidence for extra-renal 1 alpha-hydroxylation of 25-hydroxyvitamin D3 in pregnancy. Science. 1979 Jun 22;204(4399):1311–1313. doi: 10.1126/science.451538. [DOI] [PubMed] [Google Scholar]
  22. HIRSCHFELD J., LUNELL N. O. Serum protein synthesis in foetus haptoglobins and group-specific components. Nature. 1962 Dec 22;196:1220–1220. doi: 10.1038/1961220a0. [DOI] [PubMed] [Google Scholar]
  23. Haddad J. G., Birge S. J. Widespread, specific binding of 25-hydroxycholecalciferol in rat tissues. J Biol Chem. 1975 Jan 10;250(1):299–303. [PubMed] [Google Scholar]
  24. Haddad J. G., Jr, Boisseau V., Avioli L. V. Placental transfer of vitamin D3 and 25-hydroxycholecalciferol in the rat. J Lab Clin Med. 1971 Jun;77(6):908–915. [PubMed] [Google Scholar]
  25. Haddad J. G., Jr, Walgate J. Radioimmunoassay of the binding protein for vitamin D and its metabolites in human serum: concentrations in normal subjects and patients with disorders of mineral homeostasis. J Clin Invest. 1976 Nov;58(5):1217–1222. doi: 10.1172/JCI108575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Heaney R. P., Recker R. R., Saville P. D. Menopausal changes in calcium balance performance. J Lab Clin Med. 1978 Dec;92(6):953–963. [PubMed] [Google Scholar]
  28. Heaney R. P., Skillman T. G. Calcium metabolism in normal human pregnancy. J Clin Endocrinol Metab. 1971 Oct;33(4):661–670. doi: 10.1210/jcem-33-4-661. [DOI] [PubMed] [Google Scholar]
  29. Hillman L. S., Haddad J. G. Human perinatal vitamin D metabolism. I. 25-Hydroxyvitamin D in maternal and cord blood. J Pediatr. 1974 May;84(5):742–749. doi: 10.1016/s0022-3476(74)80024-7. [DOI] [PubMed] [Google Scholar]
  30. Imawari M., Goodman D. S. Immunological and immunoassay studies of the binding protein for vitamin D and its metabolites in human serum. J Clin Invest. 1977 Mar;59(3):432–442. doi: 10.1172/JCI108657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. JASANI C., NORDIN B. E., SMITH D. A., SWANSON I. SPINAL OSTEOPOROSIS AND THE MENOPAUSE. Proc R Soc Med. 1965 Jun;58:441–444. [PMC free article] [PubMed] [Google Scholar]
  32. Kawakami M., Imawari M., Goodman D. S. Quantitative studies of the interaction of cholecalciferol ((vitamin D3) and its metabolites with different genetic variants of the serum binding protein for these sterols. Biochem J. 1979 May 1;179(2):413–423. doi: 10.1042/bj1790413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Lecureuil M., Crouzat-Reynes G., Besnard J. C., Choffel C. Correlation of free thyroxine index and thyroxine: thyroxine-binding globulin ratio with the free thyroxine concentration as measured by the thyroxine and thyroxine-binding globulin radioimmunoassays. Clin Chim Acta. 1978 Aug 1;87(3):373–381. doi: 10.1016/0009-8981(78)90181-x. [DOI] [PubMed] [Google Scholar]
  35. Lester G. E., Gray T. K., Lorenc R. S. Evidence for maternal and fetal differences in vitamin D metabolism. Proc Soc Exp Biol Med. 1978 Nov;159(2):303–307. doi: 10.3181/00379727-159-40337. [DOI] [PubMed] [Google Scholar]
  36. Lund B., Selnes A. Plasma 1,25-dihydroxyvitamin D levels in pregnancy and lactation. Acta Endocrinol (Copenh) 1979 Oct;92(2):330–335. doi: 10.1530/acta.0.0920330. [DOI] [PubMed] [Google Scholar]
  37. Manolagas S. C., Anderson D. C., Lumb G. A. Glucocorticoids regulate the concentration of 1,25-dihydroxycholecalciferol receptors in bone. Nature. 1979 Jan 25;277(5694):314–315. doi: 10.1038/277314a0. [DOI] [PubMed] [Google Scholar]
  38. Recker R. R., Saville P. D., Heaney R. P. Effect of estrogens and calcium carbonate on bone loss in postmenopausal women. Ann Intern Med. 1977 Dec;87(6):649–655. doi: 10.7326/0003-4819-87-6-649. [DOI] [PubMed] [Google Scholar]
  39. Reiter E. O., Braunstein G. D., Vargas A., Root A. W. Changes in 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D during pregnancy. Am J Obstet Gynecol. 1979 Sep 15;135(2):227–229. doi: 10.1016/0002-9378(79)90349-1. [DOI] [PubMed] [Google Scholar]
  40. Riggs B. L., Jowsey J., Goldsmith R. S., Kelly P. J., Hoffman D. L., Arnaud C. D. Short- and long-term effects of estrogen and synthetic anabolic hormone in postmenopausal osteoporosis. J Clin Invest. 1972 Jul;51(7):1659–1663. doi: 10.1172/JCI106967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rosen J. F., Roginsky M., Nathenson G., Finberg L. 25-Hydroxyvitamin D. Plasma levels in mothers and their premature infants with neonatal hypocalcemia. Am J Dis Child. 1974 Feb;127(2):220–223. doi: 10.1001/archpedi.1974.02110210070009. [DOI] [PubMed] [Google Scholar]
  42. Rosenfield R. L. Plasma testosterone binding globulin and indexes of the concentration of unbound plasma androgens in normal and hirsute subjects. J Clin Endocrinol Metab. 1971 Jun;32(6):717–728. doi: 10.1210/jcem-32-6-717. [DOI] [PubMed] [Google Scholar]
  43. Rosenfield R. L. Studies of the relation of plasma androgen levels to androgen action in women. J Steroid Biochem. 1975 May;6(5):695–702. doi: 10.1016/0022-4731(75)90055-2. [DOI] [PubMed] [Google Scholar]
  44. Shenolikar I. S. Absorption of dietary calcium in pregnancy. Am J Clin Nutr. 1970 Jan;23(1):63–67. doi: 10.1093/ajcn/23.1.63. [DOI] [PubMed] [Google Scholar]
  45. Spanos E., Barrett D. I., Chong K. T., MacIntyre I. Effect of oestrogen and 1,25-dihydroxycholecalciferol on 25-hydroxycholecalciferol metabolism in primary chick kidney-cell cultures. Biochem J. 1978 Jul 15;174(1):231–236. doi: 10.1042/bj1740231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Steichen J. J., Tsang R. C., Gratton T. L., Hamstra A., DeLuca H. F. Vitamin D homeostasis in the perinatal period: 1,25-dihydroxyvitamin D in maternal, cord, and neonatal blood. N Engl J Med. 1980 Feb 7;302(6):315–319. doi: 10.1056/NEJM198002073020603. [DOI] [PubMed] [Google Scholar]
  47. Sutton A., Barltrop D. Absorption, accretion and endogenous faecal excretion of calcium by the newborn infant. Nature. 1973 Mar 23;242(5395):265–265. doi: 10.1038/242265a0. [DOI] [PubMed] [Google Scholar]
  48. Tan C. M., Raman A., Sinnathyray T. A. Serum ionic calcium levels during pregnancy. J Obstet Gynaecol Br Commonw. 1972 Aug;79(8):694–697. doi: 10.1111/j.1471-0528.1972.tb12902.x. [DOI] [PubMed] [Google Scholar]
  49. Tanaka Y., Castillo L., Wineland M. J., DeLuca H. F. Synergistic effect of progesterone, testosterone, and estradiol in the stimulation of chick renal 25-hydroxyvitamin D3-1alpha-hydroxylase. Endocrinology. 1978 Dec;103(6):2035–2039. doi: 10.1210/endo-103-6-2035. [DOI] [PubMed] [Google Scholar]
  50. Tanaka Y., Halloran B., Schnoes H. K., DeLuca H. F. In vitro production of 1,25-dihydroxyvitamin D3 by rat placental tissue. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5033–5035. doi: 10.1073/pnas.76.10.5033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Trechsel U., Bonjour J. P., Fleisch H. Regulation of the metabolism of 25-hydroxyvitamin D3 in primary cultures of chick kidney cells. J Clin Invest. 1979 Jul;64(1):206–217. doi: 10.1172/JCI109441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Tulchinsky D., Chopra I. J. Competitive ligand-binding assay for measurement of sex hormone-binding globulin (SHBG). J Clin Endocrinol Metab. 1973 Dec;37(6):873–881. doi: 10.1210/jcem-37-6-873. [DOI] [PubMed] [Google Scholar]
  53. Weisman Y., Harell A., Edelstein S., David M., Spirer Z., Golander A. 1 alpha, 25-Dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 in vitro synthesis by human decidua and placenta. Nature. 1979 Sep 27;281(5729):317–319. doi: 10.1038/281317a0. [DOI] [PubMed] [Google Scholar]
  54. Weisman Y., Vargas A., Duckett G., Reiter E., Root A. W. Synthesis of 1,25-dihydroxyvitamin D in the nephrectomized pregnant rat. Endocrinology. 1978 Dec;103(6):1992–1996. doi: 10.1210/endo-103-6-1992. [DOI] [PubMed] [Google Scholar]
  55. Williams M. L., Rose C. S., Morrow G., 3rd, Sloan S. E., Barness L. A. Calcium and fat absorption in neonatal period. Am J Clin Nutr. 1970 Oct;23(10):1322–1330. doi: 10.1093/ajcn/23.10.1322. [DOI] [PubMed] [Google Scholar]

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

RESOURCES