Duodenal calcium absorption in dexamethasone-treated mice: functional and molecular aspects.
Reduced intestinal calcium absorption may be part of the pathogenesis of glucocorticoid-induced osteoporosis. 1,25(OH)2D3 is the major regulator of the expression of the active duodenal calcium absorption genes: TRPV6 (influx), calbindin-D9K (intracellular transfer) and PMCA1b (extrusion). We investigated the influence of dexamethasone (5 days: 2 mg/kg bw) on calcium absorption in vivo and on the expression of intestinal and renal calcium transporters in calcium-deprived mice. Total and free 1,25(OH)2D3-concentrations were halved, in line with decreased 25(OH)D3-1-alpha-hydroxylase and increased 24-hydroxylase expression. Nevertheless, no difference in duodenal or renal calcium transporter expression pattern could be detected between vehicle and dexamethasone-treated mice. Accordingly, dexamethasone did not affect in vivo calcium absorption. By contrast, increased calcemia and collagen C-terminal telopeptide levels reflected increased bone resorption. Decreased osteocalcin levels suggested impaired bone formation. Hence, short-term glucocorticoid excess in young animals affected bone metabolism without detectable changes in intestinal or renal calcium handling.
Van Cromphaut
Sophie J
SJ
Laboratory of Experimental Medicine and Endocrinology (Legendo), Katholieke Universiteit Leuven, Herestraat 49, Leuven B-3000, Belgium.
Stockmans
Ingrid
I
Torrekens
Sophie
S
Van Herck
Erik
E
Carmeliet
Geert
G
Bouillon
Roger
R
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000096:biosynthesis; D000042:Absorption / Q000187:drug effects; D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism*; D002118:Calcium / Q000172:deficiency / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003907:Dexamethasone / Q000009:adverse effects* / Q000494:pharmacology; D004386:Duodenum / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005938:Glucocorticoids / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D051379:Mice; D015675:Osteocalcin / Q000378:metabolism; D010024:Osteoporosis / Q000139:chemically induced / Q000378:metabolism*
D005938:Glucocorticoids; D015675:Osteocalcin; D003907:Dexamethasone; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D000252:Calcium-Transporting ATPases; D002117:Calcitriol; D002118:Calcium