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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1989 Feb;83(2):537–542. doi: 10.1172/JCI113915

Effects of estrogen on circulating "free" and total 1,25-dihydroxyvitamin D and on the parathyroid-vitamin D axis in postmenopausal women.

C Cheema 1, B F Grant 1, R Marcus 1
PMCID: PMC303712  PMID: 2492309

Abstract

We evaluated the effect of estrogens on "free" and total calcitriol levels and on the calcitriol response to a hypocalcemic challenge in 12 postmenopausal women, age 55-74 yr. Endogenous calcitriol production was induced by intravenous Na-EDTA before and after conjugated estrogens, 1.25 mg/d for 30 d. Free calcitriol was determined by centrifugal ultrafiltration and by the molar ratio of calcitriol to vitamin D-binding protein (DBP). Estrogen increased fasting total calcitriol from 38.5 +/- 3.8 to 62.3 +/- 7.0 pg/ml (P less than 0.05). This was accompanied by a rise in free calcitriol from 104.5 +/- 11.4 to 158.7 +/- 16.4 fg/ml (P less than 0.05). Vitamin D-binding protein increased from 348 +/- 16 to 428 +/- 12 micrograms/ml (P less than 0.001), and the ratio of calcitriol/DBP increased from 1.50 +/- 0.14 to 1.94 +/- 0.18 (P less than 0.005), confirming the rise in free calcitriol. Increases in free calcitriol and in calcitriol/DBP ratios were significantly correlated, r = 0.72. Hypocalcemia led to a rapid increase in circulating immunoreactive parathyroid hormone, and to a rise in calcitriol at 24 h. The hypocalcemia-induced rise in total and free calcitriol was similar before and after estrogen, whether expressed as increments or as percent changes. We conclude that estrogen increases circulating levels of biologically active free calcitriol in postmenopausal women, but that a 30-d period of estrogen administration does not apparently improve the renal 1 alpha-hydroxylase response to a PTH challenge.

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Selected References

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  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. Bikle D. D., Gee E., Halloran B., Haddad J. G. Free 1,25-dihydroxyvitamin D levels in serum from normal subjects, pregnant subjects, and subjects with liver disease. J Clin Invest. 1984 Dec;74(6):1966–1971. doi: 10.1172/JCI111617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bikle D. D., Rasmussen H. The ionic control of 1,25-dihydroxyvitamin D3 production in isolated chick renal tubules. J Clin Invest. 1975 Feb;55(2):292–298. doi: 10.1172/JCI107932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bouillon R., Van Assche F. A., Van Baelen H., Heyns W., De Moor P. 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. J Clin Invest. 1981 Mar;67(3):589–596. doi: 10.1172/JCI110072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Buchanan J. R., Santen R., Cauffman S., Cavaliere A., Greer R. B., Demers L. M. The effect of endogenous estrogen fluctuation on metabolism of 25-hydroxyvitamin D. Calcif Tissue Int. 1986 Sep;39(3):139–144. doi: 10.1007/BF02555109. [DOI] [PubMed] [Google Scholar]
  8. Forero M. S., Klein R. F., Nissenson R. A., Nelson K., Heath H., 3rd, Arnaud C. D., Riggs B. L. Effect of age on circulating immunoreactive and bioactive parathyroid hormone levels in women. J Bone Miner Res. 1987 Oct;2(5):363–366. doi: 10.1002/jbmr.5650020502. [DOI] [PubMed] [Google Scholar]
  9. Gallagher J. C., Riggs B. L., DeLuca H. F. Effect of estrogen on calcium absorption and serum vitamin D metabolites in postmenopausal osteoporosis. J Clin Endocrinol Metab. 1980 Dec;51(6):1359–1364. doi: 10.1210/jcem-51-6-1359. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Hammond G. L., Nisker J. A., Jones L. A., Siiteri P. K. Estimation of the percentage of free steroid in undiluted serum by centrifugal ultrafiltration-dialysis. J Biol Chem. 1980 Jun 10;255(11):5023–5026. [PubMed] [Google Scholar]
  13. Henry H. L. 25(OH)D3 metabolism in kidney cell cultures: lack of a direct effect of estradiol. Am J Physiol. 1981 Feb;240(2):E119–E124. doi: 10.1152/ajpendo.1981.240.2.E119. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. Lyles K. W., Halsey D. L., Friedman N. E., Lobaugh B. Correlations of serum concentrations of 1,25-dihydroxyvitamin D, phosphorus, and parathyroid hormone in tumoral calcinosis. J Clin Endocrinol Metab. 1988 Jul;67(1):88–92. doi: 10.1210/jcem-67-1-88. [DOI] [PubMed] [Google Scholar]
  17. Maierhofer W. J., Gray R. W., Lemann J., Jr Phosphate deprivation increases serum 1,25-(OH)2-vitamin D concentrations in healthy men. Kidney Int. 1984 Mar;25(3):571–575. doi: 10.1038/ki.1984.56. [DOI] [PubMed] [Google Scholar]
  18. Manolagas S. C., Culler F. L., Howard J. E., Brickman A. S., Deftos L. J. The cytoreceptor assay for 1,25-dihydroxyvitamin D and its application to clinical studies. J Clin Endocrinol Metab. 1983 Apr;56(4):751–760. doi: 10.1210/jcem-56-4-751. [DOI] [PubMed] [Google Scholar]
  19. Marcus R., Madvig P., Young G. Age-related changes in parathyroid hormone and parathyroid hormone action in normal humans. J Clin Endocrinol Metab. 1984 Feb;58(2):223–230. doi: 10.1210/jcem-58-2-223. [DOI] [PubMed] [Google Scholar]
  20. Pike J. W., Spanos E., Colston K. W., MacIntyre I., Haussler M. R. Influence of estrogen on renal vitamin D hydroxylases and serum 1alpha,25-(OH)2D3 in chicks. Am J Physiol. 1978 Sep;235(3):E338–E343. doi: 10.1152/ajpendo.1978.235.3.E338. [DOI] [PubMed] [Google Scholar]
  21. Portale A. A., Halloran B. P., Murphy M. M., Morris R. C., Jr Oral intake of phosphorus can determine the serum concentration of 1,25-dihydroxyvitamin D by determining its production rate in humans. J Clin Invest. 1986 Jan;77(1):7–12. doi: 10.1172/JCI112304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Reinhardt T. A., Horst R. L., Orf J. W., Hollis B. W. A microassay for 1,25-dihydroxyvitamin D not requiring high performance liquid chromatography: application to clinical studies. J Clin Endocrinol Metab. 1984 Jan;58(1):91–98. doi: 10.1210/jcem-58-1-91. [DOI] [PubMed] [Google Scholar]
  23. Slovik D. M., Adams J. S., Neer R. M., Holick M. F., Potts J. T., Jr Deficient production of 1,25-dihydroxyvitamin D in elderly osteoporotic patients. N Engl J Med. 1981 Aug 13;305(7):372–374. doi: 10.1056/NEJM198108133050704. [DOI] [PubMed] [Google Scholar]
  24. Tanaka Y., Castillo L., DeLuca H. F. Control of renal vitamin D hydroxylases in birds by sex hormones. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2701–2705. doi: 10.1073/pnas.73.8.2701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tsai K. S., Heath H., 3rd, Kumar R., Riggs B. L. Impaired vitamin D metabolism with aging in women. Possible role in pathogenesis of senile osteoporosis. J Clin Invest. 1984 Jun;73(6):1668–1672. doi: 10.1172/JCI111373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Young G., Marcus R., Minkoff J. R., Kim L. Y., Segre G. V. Age-related rise in parathyroid hormone in man: the use of intact and midmolecule antisera to distinguish hormone secretion from retention. J Bone Miner Res. 1987 Oct;2(5):367–374. doi: 10.1002/jbmr.5650020503. [DOI] [PubMed] [Google Scholar]

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