This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cao, J. Articles by Vore, M. Search for Related Content PubMed PubMed Citation Articles by Cao, J. Articles by Vore, M. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Dietary Proteins

PRL, Placental Lactogen, and GH Induce Na⁺/Taurocholate-Cotransporting Polypeptide Gene Expression by Activating Signal Transducer and Activator of Transcription-5 in Liver Cells

Graduate Center for Toxicology (J.C., P.M.G., T.C.G., M.W., M.V.) and Department of Anatomy and Neurobiology (J.F.H.), College of Medicine, Chandler Medical Center, University of Kentucky, Lexington, Kentucky 40536-0305; and Department of Biology (F.T.), University of California, Santa Cruz, California 95064

Address all correspondence and requests for reprints to: Mary Vore, Graduate Center for Toxicology, 306 Health Science Research Building, University of Kentucky, Lexington, Kentucky 40536-0305. E-mail: maryv{at}pop.uky.edu

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.

This article has been cited by other articles:

				J. J. Eloranta, D. Jung, and G. A. Kullak-Ublick The Human Na+-Taurocholate Cotransporting Polypeptide Gene Is Activated by Glucocorticoid Receptor and Peroxisome Proliferator-Activated Receptor-{gamma} Coactivator-1{alpha}, and Suppressed by Bile Acids via a Small Heterodimer Partner-Dependent Mechanism Mol. Endocrinol., January 1, 2006; 20(1): 65 - 79. [Abstract] [Full Text] [PDF]

				M. Wood, M. Ananthanarayanan, B. Jones, R. Wooton-Kee, T. Hoffman, F. J. Suchy, and M. Vore Hormonal Regulation of Hepatic Organic Anion Transporting Polypeptides Mol. Pharmacol., July 1, 2005; 68(1): 218 - 225. [Abstract] [Full Text] [PDF]

				F. R. Simon, J. Fortune, M. Iwahashi, I. Qadri, and E. Sutherland Multihormonal regulation of hepatic sinusoidal Ntcp gene expression Am J Physiol Gastrointest Liver Physiol, October 1, 2004; 287(4): G782 - G794. [Abstract] [Full Text] [PDF]

				M. Matasconi, B. Angelin, and M. Rudling Pituitary control of lipoprotein and bile acid metabolism in male rats: growth hormone effects are not mediated by prolactin Am J Physiol Endocrinol Metab, July 1, 2004; 287(1): E114 - E119. [Abstract] [Full Text] [PDF]

				J. Cao, M. Wood, Y. Liu, T. Hoffman, J. Hyde, O.-K. Park-Sarge, and M. Vore Estradiol Represses Prolactin-Induced Expression of Na+/Taurocholate Cotransporting Polypeptide in Liver Cells through Estrogen Receptor-{alpha} and Signal Transducers and Activators of Transcription 5a Endocrinology, April 1, 2004; 145(4): 1739 - 1749. [Abstract] [Full Text] [PDF]

				D. Mesotten, G. Van den Berghe, C. Liddle, S. Coulter, F. McDougall, R. C. Baxter, and P. J. D. Delhanty Growth Hormone Modulation of the Rat Hepatic Bile Transporter System in Endotoxin-Induced Cholestasis Endocrinology, September 1, 2003; 144(9): 4008 - 4017. [Abstract] [Full Text] [PDF]