Association Between Intestinal Vitamin D Receptor, Calcium Absorption, and Serum 1,25 Dihydroxyvitamin D in Normal Young and Elderly Women

The exact mechanism for the decrease in intestinal calcium absorption with age is not yet understood. A decrease with age in serum 1,25‐dihydroxyvitamin D (1,25(OH)2D) or a decrease in the intestinal vitamin D receptor (VDR) protein concentration are possible causes. The objective of this study was to examine the effect of age on these factors. Fifty‐nine young women age 25–35 years were compared with 41 elderly women age 65–83 years who underwent measurements of VDR, calcium absorption using a 20 mg and 100 mg calcium carrier, and calciotropic hormones. Calcium absorption by both tests was lower in the elderly women compared with the young women (p < 0.05). Serum 1,25(OH)2D and duodenal VDR protein concentration were not significantly different between the two age groups. Serum 1,25(OH)2D correlated with the 20 mg calcium absorption test in both young (r = 0.35, p < 0.007) and elderly women (r = 0.58, p < 0.0001) and with the 100 mg calcium absorption in the elderly (r = 0.32; p < 0.05). VDR did not correlate with calcium absorption in young women or elderly women, nor did VDR correlate with serum 1,25(OH)2D and serum 25‐hydroxyvitamin D. In summary, the decrease in calcium absorption cannot be explained by a decrease in intestinal VDR. The correlation between serum 1,25(OH)2D and both calcium absorption tests only accounts for 12–30% of the variance in the age‐related change in the calcium absorption tests. Other factors, not yet understood, are responsible for the decline in calcium absorption with age.

[1]  D. Herbert,et al.  Evidence for estrogen receptor-linked calcium transport in the intestine. , 1993, Bone and mineral.

[2]  H. DeLuca,et al.  Evidence of an age-related decrease in intestinal responsiveness to vitamin D: relationship between serum 1,25-dihydroxyvitamin D3 and intestinal vitamin D receptor concentrations in normal women. , 1992, The Journal of clinical endocrinology and metabolism.

[3]  B. Komm,et al.  Dietary restriction of calcium, phosphorus, and vitamin D elicits differential regulation of the mrnas for avian intestinal calbindin‐D28K and the 1,25‐dihydroxyvitamin D3 receptor , 1992, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[4]  R. Eastell,et al.  Interrelationship among vitamin D metabolism, true calcium absorption, parathyroid function, and age in women: Evidence of an age‐related intestinal resistance to 1,25‐dihydroxyvitamin D action , 1991, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[5]  R. Civitelli,et al.  Estrogen preserves a normal intestinal responsiveness to 1,25-dihydroxyvitamin D3 in oophorectomized women. , 1990, The Journal of clinical endocrinology and metabolism.

[6]  R. Horst,et al.  Parathyroid hormone down-regulates 1,25-dihydroxyvitamin D receptors (VDR) and VDR messenger ribonucleic acid in vitro and blocks homologous up-regulation of VDR in vivo. , 1990, Endocrinology.

[7]  B. Hollis,et al.  Vitamin D status and related parameters in a healthy population: the effects of age, sex, and season. , 1990, The Journal of clinical endocrinology and metabolism.

[8]  C. Liang,et al.  Effect of age on duodenal 1,25-dihydroxyvitamin D-3 receptors in Wistar rats. , 1990, Biochimica et biophysica acta.

[9]  J. Goff,et al.  Advancing age results in reduction of intestinal and bone 1,25-dihydroxyvitamin D receptor. , 1990, Endocrinology.

[10]  J. Goff,et al.  Contrasting effects of exogenous 1,25-dihydroxyvitamin D [1,25-(OH)2D] versus endogenous 1,25-(OH)2D, induced by dietary calcium restriction, on vitamin D receptors. , 1990, Endocrinology.

[11]  H. DeLuca,et al.  An immunoradiometric assay for 1,25-dihydroxyvitamin D3 receptor. , 1989, Analytical biochemistry.

[12]  A. Norman,et al.  1,25(OH)2‐Vitamin D3 receptors: gene regulation and genetic circuitry , 1988, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[13]  M. Haussler,et al.  Evidence for in vivo upregulation of the intestinal vitamin D receptor during dietary calcium restriction in the rat. , 1988, The Journal of clinical investigation.

[14]  P. Dandona,et al.  Bone Density and Cortical Thickness in Nutritional Vitamin D Deficiency: Effect of Secondary Hyperparathyroidism , 1988, Annals of clinical biochemistry.

[15]  R. Horst,et al.  SIMPLIFIED ASSAYS FOR THE DETERMINATION OF 25-OHD, 24,25-(OH)2D AND 1,25-(OH)2D , 1988 .

[16]  Brennan,et al.  Highly sensitive two-site immunoradiometric assay of parathyrin, and its clinical utility in evaluating patients with hypercalcemia. , 1987, Clinical chemistry.

[17]  B. Hollis Assay of circulating 1,25-dihydroxyvitamin D involving a novel single-cartridge extraction and purification procedure. , 1986, Clinical chemistry.

[18]  T. Clemens,et al.  Serum vitamin D2 and vitamin D3 metabolite concentrations and absorption of vitamin D2 in elderly subjects. , 1986, The Journal of clinical endocrinology and metabolism.

[19]  D. Feldman,et al.  Homologous up-regulation of the 1,25 (OH)2 vitamin D3 receptor in rats. , 1986, Biochemical and biophysical research communications.

[20]  M. Holick,et al.  Aging decreases the capacity of human skin to produce vitamin D3. , 1985, The Journal of clinical investigation.

[21]  R. Kumar,et al.  Impaired vitamin D metabolism with aging in women. Possible role in pathogenesis of senile osteoporosis. , 1984, The Journal of clinical investigation.

[22]  S. Manolagas,et al.  The cytoreceptor assay for 1,25-dihydroxyvitamin D and its application to clinical studies. , 1983, The Journal of clinical endocrinology and metabolism.

[23]  H. DeLuca,et al.  1,25-Dihydroxyvitamin D3: short- and long-term effects on bone and calcium metabolism in patients with postmenopausal osteoporosis. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[24]  A. Norman,et al.  Effect of vitamin D status on the equilibrium between occupied and unoccupied 1,25-dihydroxyvitamin D intestinal receptors in the chick. , 1982, The Journal of clinical investigation.

[25]  H. DeLuca,et al.  Appearance of the intestinal cytosolic receptor for 1,25-dihydroxyvitamin D3 during neonatal development in the rat. , 1981, The Journal of biological chemistry.

[26]  H. DeLuca,et al.  Effect of estrogen on calcium absorption and serum vitamin D metabolites in postmenopausal osteoporosis. , 1980, The Journal of clinical endocrinology and metabolism.

[27]  B. Riggs,et al.  The effect of age on serum immunoreactive parathyroid hormone in normal and osteoporotic women. , 1980, The Journal of laboratory and clinical medicine.

[28]  H. DeLuca,et al.  Intestinal calcium absorption and serum vitamin D metabolites in normal subjects and osteoporotic patients: effect of age and dietary calcium. , 1979, The Journal of clinical investigation.

[29]  D. Galinsky,et al.  The aetiology of senile osteoporosis: secondary hyperparathyroidism due to renal failure. , 1975, The Quarterly journal of medicine.

[30]  J. Fordtran,et al.  Effect of dietary calcium and age on jejunal calcium absorption in humans studied by intestinal perfusion. , 1973, The Journal of clinical investigation.

[31]  J. Haddad,et al.  COMPETITIVE PROTEIN-BINDING RADIOASSAY FOR 25-HYDROXYCHOLECALCIFEROL1 , 1971 .

[32]  J. Gallagher,et al.  Effect of age on calcium absorption. , 1970, Lancet.

[33]  B. Hollis,et al.  In vivo effect of 17β-estradiol on intestinal calcium absorption in rats , 1994 .

[34]  X. Xu,et al.  The presence of functional estrogen receptors in intestinal epithelial cells. , 1993, Endocrinology.

[35]  J. Pike,et al.  Vitamin D3 receptors: structure and function in transcription. , 1991, Annual review of nutrition.

[36]  L. Schiller,et al.  Role of vitamin D-dependent and vitamin D-independent mechanisms in absorption of food calcium. , 1988, The Journal of clinical investigation.

[37]  B. Riggs,et al.  The influence of age on bone mineral regulating hormones. , 1986, Bone.

[38]  M. Holick Vitamin D requirements for the elderly , 1986 .

[39]  P. Hauschka,et al.  The effects of 1,25-dihydroxyvitamin D3 and dexamethasone on rat osteoblast-like primary cell cultures: receptor occupancy and functional expression patterns for three different bioresponses. , 1986, Endocrinology.

[40]  M. Haussler Vitamin D receptors: nature and function. , 1986, Annual review of nutrition.

[41]  R. Francis,et al.  Renal impairment and its effects on calcium metabolism in elderly women. , 1984, Age and ageing.

[42]  R. Horst,et al.  A microassay for 1,25-dihydroxyvitamin D not requiring high performance liquid chromatography: application to clinical studies. , 1984, The Journal of clinical endocrinology and metabolism.

[43]  H. DeLuca,et al.  Vitamin D: recent advances. , 1983, Annual review of biochemistry.

[44]  J. Haddad,et al.  Competitive protein-binding radioassay for 25-hydroxycholecalciferol. , 1971, The Journal of clinical endocrinology and metabolism.