Growth hormone modulation of the rat hepatic bile transporter system in endotoxin-induced cholestasis

Dieter Mesotten*, Greet Van den Berghe, Christopher Liddle, Sally Coulter, Fiona Mcdougall, Robert C. Baxter, Patric J. D. Delhanty

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Treatment with high dose human GH, although an effective anabolic agent, has been associated with increased incidence of sepsis, inflammation, multiple organ failure, and death in critically ill patients. We hypothesized that GH might increase mortality by exacerbating cholestasis through modulation of bile acid transporter expression. High dose GH was continuously infused over 4 d into rats, and on the final day lipopolysaccharides were injected. Hepatic bile acid transporter expression was measured by Northern analysis and immuno-blotting and compared with serum markers of cholestasis and endotoxinemia. Compared with non-GH-treated controls, GH increased endotoxin-induced markers of cholestasis and liver damage as well as augmented IL-6 induction. In endotoxinemia, GH treatment significantly induced multidrug resistance-associated protein 1 mRNA and protein and suppressed organic anion transporting polypeptides, Oatp1 and Oatp4, mRNA, suggesting impaired uptake of bilirubin and bile acids at the basolateral surface of the hepatocyte, which could contribute to the observed worsening of cholestasis by GH. This study of endotoxinemia may thus provide a mechanistic link between GH treatment and exacerbation of cholestasis through modulation of basolateral bile acid transporter expression in the rat hepatocyte.

Original languageEnglish
Pages (from-to)4008-4017
Number of pages10
JournalEndocrinology
Volume144
Issue number9
DOIs
Publication statusPublished - 1 Sep 2003
Externally publishedYes

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