Regulation of hepatic bile acid transporters Ntcp and Bsep expression.
Sodium-taurocholate cotransporting polypeptide (Ntcp) and bile salt export pump (Bsep) are two key transporters for hepatic bile acid uptake and excretion. Alterations in Ntcp and Bsep expression have been reported in pathophysiological conditions. In the present study, the effects of age, gender, and various chemicals on the regulation of these two transporters were characterized in mice. Ntcp and Bsep mRNA levels in mouse liver were low in the fetus, but increased to its highest expression at parturition. After birth, mouse Ntcp and Bsep mRNA decreased by more than 50%, and then gradually increased to adult levels by day 30. Expression of mouse Ntcp mRNA and protein exhibit higher levels in female than male livers. No gender difference exists in BSEP/Bsep expression in human and mouse livers. Hormone replacements conducted in gonadectomized, hypophysectomized, and lit/lit mice indicate that female-predominant Ntcp expression in mouse liver is due to the inhibitory effect of male-pattern GH secretion, but not sex hormones. Ntcp and Bsep expression are in general resistant to induction by a large battery of microsomal enzyme inducers. Administration of cholestyramine increased Ntcp, whereas chenodeoxycholic acid (CDCA) increased Bsep mRNA expression. In conclusion, mouse Ntcp and Bsep are regulated by age, gender, cholestyramine, and bile acid, but resistant to induction by most microsomal enzyme inducers.
Cheng
Xingguo
X
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Buckley
David
D
Klaassen
Curtis D
CD
D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D015153:Blotting, Western; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D002784:Cholesterol / Q000494:pharmacology; D002792:Cholestyramine Resin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D013006:Growth Hormone / Q000494:pharmacology; D006801:Humans; D007016:Hypophysectomy; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics* / Q000378:metabolism; D010052:Ovariectomy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012737:Sex Factors; D027981:Symporters / Q000235:genetics* / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; D027981:Symporters; D013196:Dihydrotestosterone; D002635:Chenodeoxycholic Acid; D002792:Cholestyramine Resin; C071908:sodium-bile acid cotransporter; D004958:Estradiol; D003907:Dexamethasone; D013006:Growth Hormone; D002784:Cholesterol