PRL, placental lactogen, and GH induce NA(+)/taurocholate-cotransporting polypeptide gene expression by activating signal transducer and activator of transcription-5 in liver cells.
We investigated the transcriptional regulation of the Na(+)/taurocholate cotransporting polypeptide gene by PRL, placental lactogen, and GH. In primary hepatocytes, ovine PRL induced a dose-dependent phosphorylation and nuclear translocation of signal transducers and activators of transcription-5a and -5b, but not -1 or -3, whereas mouse placental lactogen I and rat GH activated -5a, -5b, and -1. In EMSAs, ovine PRL, mouse placental lactogen I, and rat GH increased the specific DNA binding of nuclear signal transducer and activator of transcription-5 to its consensus element in both transfected HepG2 cells and primary hepatocytes. PRL, placental lactogen I, and GH also increased Na(+)/taurocholate cotransporting polypeptide mRNA expression in hepatocytes from control and pregnant (mouse placental lactogen I) rats. Genistein, a phosphotyrosine kinase inhibitor, inhibited PRL-induced signal transducer and activator of transcription-5 activation and Na(+)/taurocholate-cotransporting polypeptide mRNA. In HepG2 cells transiently cotransfected with either the long form of the rat PRL receptor or rat GH receptor, signal transducer and activator of transcription-5a and a -5-responsive luciferase expression vector containing the Na(+)/taurocholate-cotransporting polypeptide promoter, mouse placental lactogen I, like ovine PRL, activated -5a via the long form of the rat PRL receptor; whereas rat GH activated -5a via rat GH receptor, leading to transactivation of the Na(+)/taurocholate-cotransporting polypeptide promoter. These data establish that PRL and placental lactogen I induce Na(+)/taurocholate-cotransporting polypeptide gene expression via signal transducer and activator of transcription-5 proteins in liver, and indicate that these hormones play an important role in regulating liver metabolic function.
Cao
J
J
Graduate Center for Toxicology, College of Medicine, Chandler Medical Center, University of Kentucky, Lexington, Kentucky 40536-0305, USA.
Gowri
P M
PM
Ganguly
T C
TC
Wood
M
M
Hyde
J F
JF
Talamantes
F
F
Vore
M
M
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology; D008099:Liver / Q000502:physiology*; D026901:Membrane Transport Proteins; D008894:Milk Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D010928:Placental Lactogen / Q000494:pharmacology; D011388:Prolactin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050799:STAT5 Transcription Factor; D027981:Symporters; D015534:Trans-Activators / Q000502:physiology*; D015533:Transcriptional Activation / Q000187:drug effects
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D026901:Membrane Transport Proteins; D008894:Milk Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D050799:STAT5 Transcription Factor; D027981:Symporters; D015534:Trans-Activators; C071908:sodium-bile acid cotransporter; D011388:Prolactin; D013006:Growth Hormone; D010928:Placental Lactogen