AJP - Endocrinology and Metabolism, Vol 258, Issue 2 E282-E287, Copyright © 1990 by American Physiological Society
Low-calcium diets increase both production and clearance of 1,25-dihydroxyvitamin D3 in rats
J. Fox, J. E. Bunker, M. Kamimura and P. F. Wong
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Administration of large doses of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] to
animals induces 1,25(OH)2D3 side-chain oxidative pathways. This study
determined if the elevated plasma 1,25(OH)2D3 seen in rats fed low-Ca diets
is associated not only with an increased production rate (PR) but also with
an increased metabolic clearance rate (MCR) of the hormone. In vitamin
D-replete rats fed a Ca-deficient diet for 3-4 wk, the PR increased
21-fold, plasma levels 15-fold, and the MCR by 37%. The increased MCR in
Ca-deficient rats was associated with a 48% increase in hepatic microsomal
UDP glucuronyl transferase enzyme activity, whereas 1,25(OH)2D3 catabolism
by homogenates of liver and small intestinal mucosa was unchanged. In
contrast to the effects of low-Ca diets, acute (7 h) pharmacological
elevation of plasma 1,25(OH)2D3 to 1.5 ng/ml in normal rats did not
influence the MCR. Thus chronically elevated 1,25(OH)2D3 levels are
necessary to stimulate clearance. In conclusion, 1,25(OH)2D3 clearance in
rats can be stimulated not only by chronic pharmacological doses of
1,25(OH)2D3 but also by the physiological stimulus of a low-Ca diet. Hence,
plasma 1,25(OH)2D3 levels can be regulated by changes in both PR and MCR.
