Effects of 1,25-Dihydroxycholecalciferol on Intestinal Calcium Transport in Cortisone-Treated Rats

Abstract

A B S T R A C T The administration of glucocorticoids may decrease intestinal calcium absorption in vivo and the active transport of calcium in rat duodenum in vitro. It has been suggested that this apparent "anti-vitamin D-like" effect of steroid hormones may be related to alterations in vitamin D metabolism. In order to test this hypothesis, vitamin D-deficient control and cortisone-treated rats were given an intraperitoneal injection of 5.5 IU of 1,25-dihydroxycholecalciferol (1,25-DHCC), the probable end-organ active vitamin D metabolite in the intestine, and 16 h later studies of duodenal calcium transport were performed in modified Ussing chambers. In the vitamin D-deficient state, cortisone administration was associated with a diminution in Jms, JNet, and the flux ratio (Jms/JsM). While the magnitude of the increases in Jms and JNet that resulted fromi 1,25-DHCC treatment were approximately the same in control and cortisone-treated animals, 1,25-DHCC failed to restore these parameters to "normal levels" in the steroid-treated rats. Furthermore, contrary to the results obtained in the saline-treated controls, 1,25-DHCC failed to reduce Jsm in the duodenum from cortisone-treated rats. The cortisone-related defect in calcium transport was due to alterations in both unidirectional calcium fluxes (decrease in Jms and increase in Jsm), such that the JNet and the flux ratio (Jms/Jsm) were only approximately 50% of the levels achieved in vitamin D-deficient control animals repleted with the same dose of 1,25-DHCC.

Production, degradation, and circulating levels of 1,25-dihydroxyvitamin D in health and in chronic glucocorticoid excess.

“…Moreover, serum 25-OH-D has been reported to be normiial (14,15), andl serum 1,25(OH)2D hats eveni been reporte(l to be increased by glucocorticoicl excess in certain experimental models (4,16). Others (16)(17)(18)(19)(20) have postulated a ldirect effect of supraphysiologic doses of glucocorticoids on gut that is independent of vitaimin D metabolism.…”

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

“…Favus et al (8), using 1.25X10-1 1.25X10-2 FIGURE 5 Jnet of calcium across distal colon from dexamethasone-treated (light columns) and 1,25(OH)2D3-treated (dark columns) rats. Measurements were made in buffers with three different calcium concentrations.…”

“…Measurements were made in buffers with three different calcium concentrations. (5)(6)(7)(8)(9) while in the more distal small bowel Ca transport was either not altered (6,9) or stimulated (7). In glucocorticoid-treated man the absorption of orally administered radioactive Ca was slower than in untreated subjects in the first hour, similar at around the second hour, and thereafter the absorption was better in the treated than the untreated subjects (16,25).…”

“…Because a number of studies have reported a suppressive effect of glucocorticoids on duodenal Ca absorption (5)(6)(7)(8)(9), in this study we examined the effect of a glucocorticoid (dexamethasone) on colonic Ca transport. Rather unexpectedly, we found that this hormone stimulated Ca absorption in rat distal colon, further stressing the segmental differences in intestinal Ca transport processes.…”

Evidence for in vivo upregulation of the intestinal vitamin D receptor during dietary calcium restriction in the rat.

“…Small intestinal absorption of dietary calcium occurs by a paracellular pathway driven by osmotic and concentration gradients and a cellular active transport process that is regu-lated by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] (1)(2)(3). The intestinal actions of 1,25(OH)2D3 occur through a complex serjes of events that are initiated by binding of the steroid hormone to a specific intracellular protein, the vitamin D receptor (4)(5)(6)(7).…”