Inhibition of growth hormone action in models of inflammation

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

Research output: Contribution to journalArticle

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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)
JournalAmerican Journal of Physiology - Cell Physiology
Volume279
Issue number6 48-6
StatePublished - Dec 28 2000

Fingerprint

Growth Hormone
Inflammation
Serine Proteinase Inhibitors
STAT5 Transcription Factor
Lipopolysaccharides
Hepatocytes
Interleukin-1
Liver
Tumor Necrosis Factor-alpha
Response Elements
Conditioned Culture Medium
Monocytes
Interleukin-6
Cytokines
Messenger RNA
Genes

Keywords

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

Cite this

Bergad, P. L., Schwarzenberg, S. J., Humbert, J. T., Morrison, M., Amarasinghe, S., Towle, H. C., & Berry, S. A. (2000). Inhibition of growth hormone action in models of inflammation. American Journal of Physiology - Cell Physiology, 279(6 48-6).

Inhibition of growth hormone action in models of inflammation. / Bergad, Pearl L.; Schwarzenberg, Sarah J; Humbert, Jeffrey T.; Morrison, Michelle; Amarasinghe, Sherani; Towle, Howard C.; Berry, Susan A.

In: American Journal of Physiology - Cell Physiology, Vol. 279, No. 6 48-6, 28.12.2000.

Research output: Contribution to journalArticle

Bergad, PL, Schwarzenberg, SJ, Humbert, JT, Morrison, M, Amarasinghe, S, Towle, HC & Berry, SA 2000, 'Inhibition of growth hormone action in models of inflammation', American Journal of Physiology - Cell Physiology, vol. 279, no. 6 48-6.
Bergad PL, Schwarzenberg SJ, Humbert JT, Morrison M, Amarasinghe S, Towle HC et al. Inhibition of growth hormone action in models of inflammation. American Journal of Physiology - Cell Physiology. 2000 Dec 28;279(6 48-6).
Bergad, Pearl L. ; Schwarzenberg, Sarah J ; Humbert, Jeffrey T. ; Morrison, Michelle ; Amarasinghe, Sherani ; Towle, Howard C. ; Berry, Susan A. / Inhibition of growth hormone action in models of inflammation. In: American Journal of Physiology - Cell Physiology. 2000 ; Vol. 279, No. 6 48-6.
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