TY - JOUR
T1 - Inhibition of growth hormone action in models of inflammation
AU - Bergad, Pearl L.
AU - Schwarzenberg, Sarah Jane
AU - Humbert, Jeffrey T.
AU - Morrison, Michelle
AU - Amarasinghe, Sherani
AU - Towle, Howard C.
AU - Berry, Susan A.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Lipopolysaccharide
KW - Rat liver
KW - Serine protease inhibitors 2.1 and 2.2
KW - Signal transducers and activators of transcription proteins
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U2 - 10.1152/ajpcell.2000.279.6.c1906
DO - 10.1152/ajpcell.2000.279.6.c1906
M3 - Article
C2 - 11078706
AN - SCOPUS:0033635102
SN - 0363-6143
VL - 279
SP - C1906-C1917
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 6 48-6
ER -