Dietary restriction of calcium, phosphorus, and vitamin D elicits differential regulation of the mRNAs for avian intestinal calbindin-D28k and the 1,25-dihydroxyvitamin D3 receptor.
We investigated the regulation of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-induced calbindin-D28k (CaBP) and of the vitamin D receptor (VDR) by evaluating CaBP protein, CaBP mRNA, and VDR mRNA under conditions of altered intake of vitamin D, calcium, or phosphorus. Chickens were maintained for 10 days on one of four diets: vitamin D-deficient, normal (1.0% Ca and 1.1% P), low calcium (0.1% Ca and 1.2% P), and low phosphorus (1.1% Ca and 0.3% P). CaBP was undetectable in D-deficient duodena and was elevated above normal values by low-calcium (3.1-fold) and low-phosphorus (2.3-fold) intake. Contradictory to published data, we observed a correlation between CaBP protein and mRNA levels in that the CaBP mRNA was absent in D-deficient intestine and augmented threefold and twofold in low-calcium and low-phosphate duodena, respectively. In contrast, VDR mRNA concentrations were identical in vitamin D-deficient and normal duodena, implying that intestinal VDR is not dependent upon 1,25-(OH)2D3 for basal expression. Chickens fed a low-phosphorus diet displayed a twofold increase in VDR mRNA, but those fed a low-calcium diet exhibited a dramatic decrease in VDR mRNA. These data show that CaBP mRNA and protein levels are modulated in a tightly coupled fashion, and they are consistent with previous conclusions that augmented circulating 1,25-(OH)2D3 stimulates CaBP expression when dietary calcium or phosphorus is limiting. However, a more complex regulation of VDR expression occurs in that low-phosphorus restriction enhances VDR mRNA levels, possibly via increased circulating 1,25-(OH)2D3. Conversely, reduced dietary calcium diminishes VDR mRNA despite increased circulating 1,25-(OH)2D3, indicating that another factor, such as parathyroid hormone, is a predominant downregulator of VDR.
Meyer
J
J
Department of Biochemistry, College of Medicine, University of Arizona, Tucson.
Fullmer
C S
CS
Wasserman
R H
RH
Komm
B S
BS
Haussler
M R
MR
D000818:Animals; D015152:Blotting, Northern; D064026:Calbindins; D002117:Calcitriol; D002136:Calcium, Dietary / Q000008:administration & dosage*; D002645:Chickens; D004386:Duodenum / Q000737:chemistry; D016226:Phosphorus, Dietary / Q000008:administration & dosage*; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000378:metabolism*; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000235:genetics; D064030:S100 Calcium Binding Protein G / Q000235:genetics; D014807:Vitamin D / Q000008:administration & dosage*
D064026:Calbindins; D002136:Calcium, Dietary; D016226:Phosphorus, Dietary; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D064030:S100 Calcium Binding Protein G; D014807:Vitamin D; D012313:RNA; D002117:Calcitriol