Influence of Adrenal Steroids on Radio-Calcium Metabolism in Young Beagle Dogs

260

A B S T R A C T It is generally recognized that glucocorticoid administration may diminish calcium absorption in vivo as well as the active transport of calcium by the intestine in vitro. Recent studies by others have emphasized the possibility of an alteration in the metabolism of vitamin D to 25-hydroxycholecalciferol in accounting for the steroid effects on calcium absorption. The results obtained in the present studies fail to support this hypothesis.The present studies confirm that the administration of cortisone or other glucocorticoids to the rat interferes with the active transport of calcium by duodenal gut sacs in vitro. This abnormality is not due to an alteration in the permeability of the intestine to calcium, and it cannot be corrected by the administration of either massive doses of vitamin D3 or modest doses of 25-hydroxycholecalciferol. Experiments concerned with the effects of cortisone on the level of the vitamin D-dependent duodenal calcium-binding protein, the amount of bioassayable vitamin D activity in the mucosa, and the distribution and metabolism of 'H-vitamin D3, did not provide evidence in favor of a hormone-related defect in either the localization of vitamin D or its metabolism to 25-hydroxycholecalciferol. Alterations in the transport of iron and D-galactose, not dependent on vitamin D, suggest that cortisone treatment may be responsible for more than a simple antagonism to the effects of vitamin D.The results of the present studies indicate that cortisone administration affects the cellular mechanisms mediating calcium transport in a manner that is opposite to the

Section: Methodscontrasting

confidence: 72%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of cortisone treatment on the active transport of calcium by the small intestine

Kimberg¹,

Baerg²,

Gershon³

et al. 1971

260

“…Fig. 5 (21), rats (20), and dogs (22), although in our study dexamethasone did not alter colonic Ca secretion. The data of Ferretti et al (21) may explain, at least in part, the divergent findings on the effect of glucocorticoids on intestinal Ca absorption.…”

Section: Resultscontrasting

confidence: 42%

Unanticipated stimulatory action of glucocorticoids on epithelial calcium absorption. Effect of dexamethasone on rat distal colon.

Lee¹

1983

A B S T R A C T We studied the action of a glucocorticoid (GC, dexamethasone) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on transepithelial calcium (Ca) transport in rat distal colon. GC 1.2 mg or 1,25(OH)2D3 270 ng were given daily for 4 d and Ca fluxes were measured in vitro in the absence of electrochemical gradients (Ussing technique). Results: (a) Both 1,25(OH)2D3 and GC increased Ca absorptive flux from 24±3 (SEM) to 50±1 and from 23±1 to 38±4 nmol/cm2 per h, respectively (in each case n = 9, P < 0.01); both steroid hormones had no effect on Ca secretory flux. (b) GC, but not 1,25(OH)2D3 increased the short-circuit current (Isc) from 30±5; to 111±13 MA/cm2 (P < 0.01), reflecting stimulation of electrogenic sodium (Na) transport. Choline replacement of Na in the bathing buffer abolished both the Isc and the active Ca transport induced by GC, but has no effect on the 1,25(OH)2D3-stimulated active Ca absorption. (c) When the buffer Ca concentration ([Ca]) on both sides of the epithelium was reduced from 1.25 to 1.25 X 10-2 mM, the GC-induced, but not the 1,25(OH)2D3-induced, stimulation in Ca absorption was abolished. This suggests that the GC-stimulated Ca absorption may require a "threshold" Ca gradient across the luminal membrane through which Ca influx occurs. Thus, contrary to the current consensus, this study demonstrates that GC stimulates active Ca transport and that this action is mediated through a mechanism dependent on the presence of Na and a critical [Ca] in the ambient medium.

“…Pharmacologic doses of corticosteroids impair intestinal absorption of calcium (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) and result in a negative calcium balance (4,(9)(10)(11), which may contribute to the development of osteoporosis. It has been postulated that corticosteroids decrease intestinal calcium absorption either by interfering with the metabolic activation of vitamin D or by antagonizing, directly or indirectly, the effects of vitamin D on the gut, or by both mechanisms (12).…”

Section: Introductionmentioning

confidence: 99%

Intestinal Calcium Absorption in Exogenous Hypercortisonism

Klein¹,

Arnaud²,

Gallagher³

et al. 1977

334

A B S T R A C T Pharmacologic doses of corticosteroids impair intestinal calcium absorption and contribute to negative calcium balance. However, the relationship between the impaired calcium absorption and a possible defect in the conversion of vitamin D to its physiologically active form, 1,25-dihydroxyvitamin D, is unknown. We compared fractional calcium absorption (double-isotope method, 100-mg carrier) and serum 25-hydroxyvitamin D (25-OH-D) (Haddad method) in 27 patients receiving pharmacologic doses of prednisone with 27 age-, sex-, and season-matched normal subjects. In patients receiving high daily doses of prednisone (15-100 mg/day), calcium absorption (P < 0.02) and serum 25-OH-D (P < 0.001) were decreased. However, in patients receiving low doses (8-10 mg/ day) or high doses (30-100 mg) of prednisone on an alternate-day schedule, both of these parameters were normal. Calcium absorption in the patients treated with daily prednisone correlated inversely with the dose ofcorticosteroids (r = -0.52, P < 0.025) and, in all steroid-treated patients, correlated directly with serum 25-OH-D (r = 0.58, P < 0.01). In four patients who received high-dose corticosteroid therapy for an average of 4 wk, serum 25-OH-D decreased by 35.5% from pretreatment values. Administration of a physiologic or near-physiologic dose of synthetic 1,25-dihydroxyvitamin D3 (0.4 ,ug