Inhibition of growth hormone action in models of inflammation

Pearl L. Bergad, Sarah Jane Schwarzenberg, Jeffrey T. Humbert, Michelle Morrison, Sherani Amarasinghe, Howard C. Towle, Susan A. Berry

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Growth hormone (GH) action is attenuated during the hepatic acutephase response (APR). To understand this attenuation, we asked whether GH and cytokine-signaling pathways intersect during an APR. In hypophysectomized rats treated with lipopolysaccharide (LPS), accumulation of activated signal transducer and transcription activator 5 (Stat5) in hepatic nuclei in response to GH and its binding to a GH response element (GHRE) from the serine protease inhibitor (Spi) 2.1 promoter are diminished in a time-dependent manner. Similarly, accumulation of activated Star3 in hepatic nuclei in response to LPS and its binding to a high-affinity sis-inducible element (SIE) are also diminished by the simultaneous administration of GH. In functional assays with primary hepatocytes, LPS-stimulated monocyte-conditioned medium (MoCM) inhibits the GH response of Stat5-dependent Spi 2.1 reporter activity but induces Stat3-dependent Spi 2.2 reporter activity, as in an APR. Similar results are obtained when hepatocytes are treated with either tumor necrosis factor-α (TNF-α) or interleukin (IL)-1β. TNF-α, IL-1β, and IL-6 also inhibit. GH-induced Spi 2.1 mRNA expression in hepatocytes. Thus inhibition of the GH signaling pathway during an APR results in reduced expression of GH-responsire genes.

Original languageEnglish (US)
Pages (from-to)C1906-C1917
JournalAmerican Journal of Physiology - Cell Physiology
Volume279
Issue number6 48-6
DOIs
StatePublished - 2000

Keywords

  • Lipopolysaccharide
  • Rat liver
  • Serine protease inhibitors 2.1 and 2.2
  • Signal transducers and activators of transcription proteins

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