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.
Although aged rats reportedly have reduced intestinal vitamin D receptor (VDR) concentrations, it is unclear whether an analogous age-related defect occurs in man. Thus, we assessed the interrelationship among serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], calcium absorption and intestinal VDR in 44 healthy, ambulatory women, ages 20-87 yr. Fractional calcium absorption was measured after oral administration of 45Ca (20 mg CaCl2 as carrier); serum 1,25-(OH)2D3, by the calf thymus binding assay; and serum intact PTH, by a two-site immunochemiluminometric assay. Vitamin D receptor concentration was measured, by a new immunoradiometric assay, in biopsy specimens taken from the second part of the duodenum during gastroduodenoscopy in 35 of the women. Despite an age-related increase in serum PTH (r = 0.48; P less than 0.001) and in serum 1,25-(OH)2D3 concentration (r = 0.32; P less than 0.05), intestinal VDR concentration decreased with age (r = -0.38; P = 0.03) and fractional calcium absorption did not change with age. Although a contribution of decreased 25-hydroxyvitamin D 1 alpha-hydroxylase activity to the blunting of the increase in serum 1,25-(OH)2D3 concentration late in life is not excluded, the data are far more consistent with impaired intestinal responsiveness to 1,25-(OH)2D3 action. This defect could lead to compensatory increases in PTH secretion and 1,25-(OH)2D3 production which maintain calcium absorption and serum ionic calcium, but at the expense of increased bone loss.
Ebeling
P R
PR
Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905.
Sandgren
M E
ME
DiMagno
E P
EP
Lane
A W
AW
DeLuca
H F
HF
Riggs
B L
BL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D007422:Intestines / Q000648:ultrastructure*; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D011863:Radioimmunoassay; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000032:analysis*; D012044:Regression Analysis
D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D003404:Creatinine; D002117:Calcitriol; D002118:Calcium