Lithocholic acid can carry out in vivo functions of vitamin D.
The physiological ligand for the vitamin D receptor (VDR) is 1,25-dihydroxyvitamin D(3). Lithocholic acid (LCA), a bile acid implicated in the progression of colon cancer, was recently shown to bind to VDR with low affinity and increase expression of the xenobiotic enzymes of the CYP3A family. Thus, LCA can induce its own catabolism through the VDR. We have now found that LCA can substitute for vitamin D in the elevation of serum calcium in vitamin D-deficient rats. Further, LCA in the diet will also replace vitamin D in the mobilization of calcium from bone. Further, LCA induces CYP24-hydroxylase mRNA gene expression in the kidney of vitamin D-deficient rats. It is clear, therefore, that LCA can be absorbed into the circulation to bind to the VDR at extra-intestinal sites. These findings lend support for the idea that the VDR may have evolved from an original role in detoxification.
Nehring
Jamie A
JA
Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, WI 53706, USA.
Zierold
Claudia
C
DeLuca
Hector F
HF
D000818:Animals; D064026:Calbindins; D002118:Calcium / Q000097:blood; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003902:Detergents / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000201:enzymology; D007668:Kidney / Q000201:enzymology / Q000378:metabolism; D008095:Lithocholic Acid / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013045:Species Specificity; D013250:Steroid Hydroxylases / Q000096:biosynthesis* / Q000235:genetics; D050916:TRPV Cation Channels / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000178:diet therapy*; D065668:Vitamin D3 24-Hydroxylase
D064026:Calbindins; D003902:Detergents; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D064030:S100 Calcium Binding Protein G; D050916:TRPV Cation Channels; C120776:TRPV6 channel; D008095:Lithocholic Acid; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D000252:Calcium-Transporting ATPases; D002118:Calcium