Decreased intestinal calcium absorption in vivo and normal brush border membrane vesicle calcium uptake in cortisol-treated chickens: evidence for dissociation of calcium absorption from brush border vesicle uptake.

Abstract

The influence of cortisol on intestinal calcium transport was studied in isolated duodenal loops and brush border membrane (BBM) vesicles ofvitamin D-deficient or replete chickens. Four-to five-week-old vitamin D-deficient cockerels were dosed intraperitoneally with 1 pg of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] alone 15 hr before sacrifice or in combination with 1, 3, or 5 mg of cortisol 24 and 48 hr before sacrifice. After a 1-pzg dose of 1,25-(OH)2D3 the in situ intestinal ligated loop technique revealed a 60% increase in calcium absorption compared to control birds (P c 0.001). However, the administration of cortisol in various doses (3 and 5 mg) to chickens given 1,25-(OH)2D3 resulted in significant decreases in intestinal calcium transport in vivo (P -0.05; P c 0.05). When intestinal BBM vesicles were prepared from birds treated in a manner identical with that described above, there was no observable difference between calcium uptake in BBM vesicles of the 1,25-(OH)2D3-treated birds and that of the cortisol plus 1,25-(OH)AD3-treated birds. 1,25-(OH)2D3-treated and 1,25-(OH)2D3 plus cortisol-treated chicks had intestinal BBM vesicle uptakes that were significantly greater than those of vitamin D-deficient controls (P c 0.02; P 5 0.025).These data show that in vivo intestinal calcium transport may be markedly reduced in the presence of normal intestinal BBM vesicle calcium uptake. This suggests that factors other than BBM calcium uptake (e.g., protein synthesis or contraluminal membrane events) play an important role in the movement of calcium from the intestinal lumen into the bloodstream and extracellular fluid of the organism.Vitamin D3 via its active metabolite, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], is responsible for the active transport of calcium in the proximal intestine (1-3). Much has been learned in recent years of the metabolism ofvitamin D, but the precise cellular and molecular scheme of events leading to increased intestinal calcium transport remains unknown. It is known, for example, that 1,25-(OH)2D3 is rapidly localized to the nucleus of intestinal cells (4)(5)(6)(7)(8). In all likelihood, 1,25-(OH)2D3 enters the cell and associates with a cytosolic binding protein (9,10) prior to translocation into the nucleus (11). In the nucleus it increases RNA polymerase II activity (11), RNA synthesis (12) The publication costs ofthis article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

The negative effect of dexamethasone on calcium-processing gene expressions is associated with a glucocorticoid-induced calcium-absorbing disorder

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TRPV6 is not required for 1α,25-dihydroxyvitamin D 3 -induced intestinal calcium absorption in vivo

“…We and others suggested the involvement of vitamin D in the regulation of paracellular calcium transport in the intestine (6,7,19,20). From a microarray study in rats, it seemed likely that vitamin D regulates tight junction permeability in intestine by regulating expression of several tight junction proteins including claudin-3 (6).…”

Glucocorticoid-Induced Osteoporosis: From Basic Mechanisms to Clinical Aspects

“…The mechanisms responsible for GC-induced inhibition of the active transcellular transport of calcium in the intestine are poorly understood. GCs do not alter the initial uptake of calcium by the brush border membrane vesicles [127] . Synthesis of calcium binding protein is decreased by GCs, whereas calcium release by mitochondria appears to be inhibited because of mitochondrial ATP depletion [128] .…”