Acute Nuclear Actions of Growth Hormone (GH): Cycloheximide Inhibits Inducible Activator Protein-1 Activity, but Does Not Block GH-Regulated Signal Transducer and Activator of Transcription Activation or Gene Expression

Ann M. Gronowski, Catherine Le Stunff, Peter Rotwein

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The mechanisms by which GH regulates gene expression to stimulate somatic growth and alter intermediary metabolism are unknown. We have shown previously that in vivo GH administration rapidly modifies the tyrosine phosphorylation of multiple hepatic nuclear proteins, including the inducible transcription factors, Stat1, Stat3, and (in this report) Stat5, and have found that hormone treatment also rapidly alters gene transcription in the liver. In this study, we have used the protein synthesis inhibitor, cycloheximide (CHX), to investigate which of the acute actions of GH are primary hormonal responses and which require concurrent protein synthesis. We found that many of the early changes in nuclear protein tyrosine phosphorylation and in nuclear protein-DNA binding after GH are not blunted by CHX. The activation of insulin-like growth factor I and Spi 2.1 gene expression and the inhibition of albumin transcription also are not blocked by CHX, suggesting that these effects are primary consequences of GH-activated signal transduction pathways. By contrast, CHX completely inhibits the induction of activator protein-1 DNA-binding activity by GH, indicating that this action is secondary to the stimulation of Fos and/or Jun protein biosynthesis. Our results support the idea that multiple primary and secondary signaling pathways contribute to the pleiotropic effects of GH on gene expression and provide a framework for delineating the mechanisms controlling the acute actions of GH.

Original languageEnglish (US)
Pages (from-to)55-64
Number of pages10
JournalEndocrinology
Volume137
Issue number1
StatePublished - 1996
Externally publishedYes

Fingerprint

Transcription Factor AP-1
Cycloheximide
Transducers
Transcriptional Activation
Growth Hormone
Gene Expression
Nuclear Proteins
Tyrosine
Phosphorylation
Protein Synthesis Inhibitors
Liver
DNA
Protein Biosynthesis
Insulin-Like Growth Factor I
Protein Binding
Albumins
Signal Transduction
Transcription Factors
Hormones
Growth

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

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title = "Acute Nuclear Actions of Growth Hormone (GH): Cycloheximide Inhibits Inducible Activator Protein-1 Activity, but Does Not Block GH-Regulated Signal Transducer and Activator of Transcription Activation or Gene Expression",
abstract = "The mechanisms by which GH regulates gene expression to stimulate somatic growth and alter intermediary metabolism are unknown. We have shown previously that in vivo GH administration rapidly modifies the tyrosine phosphorylation of multiple hepatic nuclear proteins, including the inducible transcription factors, Stat1, Stat3, and (in this report) Stat5, and have found that hormone treatment also rapidly alters gene transcription in the liver. In this study, we have used the protein synthesis inhibitor, cycloheximide (CHX), to investigate which of the acute actions of GH are primary hormonal responses and which require concurrent protein synthesis. We found that many of the early changes in nuclear protein tyrosine phosphorylation and in nuclear protein-DNA binding after GH are not blunted by CHX. The activation of insulin-like growth factor I and Spi 2.1 gene expression and the inhibition of albumin transcription also are not blocked by CHX, suggesting that these effects are primary consequences of GH-activated signal transduction pathways. By contrast, CHX completely inhibits the induction of activator protein-1 DNA-binding activity by GH, indicating that this action is secondary to the stimulation of Fos and/or Jun protein biosynthesis. Our results support the idea that multiple primary and secondary signaling pathways contribute to the pleiotropic effects of GH on gene expression and provide a framework for delineating the mechanisms controlling the acute actions of GH.",
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T2 - Cycloheximide Inhibits Inducible Activator Protein-1 Activity, but Does Not Block GH-Regulated Signal Transducer and Activator of Transcription Activation or Gene Expression

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AU - Le Stunff, Catherine

AU - Rotwein, Peter

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N2 - The mechanisms by which GH regulates gene expression to stimulate somatic growth and alter intermediary metabolism are unknown. We have shown previously that in vivo GH administration rapidly modifies the tyrosine phosphorylation of multiple hepatic nuclear proteins, including the inducible transcription factors, Stat1, Stat3, and (in this report) Stat5, and have found that hormone treatment also rapidly alters gene transcription in the liver. In this study, we have used the protein synthesis inhibitor, cycloheximide (CHX), to investigate which of the acute actions of GH are primary hormonal responses and which require concurrent protein synthesis. We found that many of the early changes in nuclear protein tyrosine phosphorylation and in nuclear protein-DNA binding after GH are not blunted by CHX. The activation of insulin-like growth factor I and Spi 2.1 gene expression and the inhibition of albumin transcription also are not blocked by CHX, suggesting that these effects are primary consequences of GH-activated signal transduction pathways. By contrast, CHX completely inhibits the induction of activator protein-1 DNA-binding activity by GH, indicating that this action is secondary to the stimulation of Fos and/or Jun protein biosynthesis. Our results support the idea that multiple primary and secondary signaling pathways contribute to the pleiotropic effects of GH on gene expression and provide a framework for delineating the mechanisms controlling the acute actions of GH.

AB - The mechanisms by which GH regulates gene expression to stimulate somatic growth and alter intermediary metabolism are unknown. We have shown previously that in vivo GH administration rapidly modifies the tyrosine phosphorylation of multiple hepatic nuclear proteins, including the inducible transcription factors, Stat1, Stat3, and (in this report) Stat5, and have found that hormone treatment also rapidly alters gene transcription in the liver. In this study, we have used the protein synthesis inhibitor, cycloheximide (CHX), to investigate which of the acute actions of GH are primary hormonal responses and which require concurrent protein synthesis. We found that many of the early changes in nuclear protein tyrosine phosphorylation and in nuclear protein-DNA binding after GH are not blunted by CHX. The activation of insulin-like growth factor I and Spi 2.1 gene expression and the inhibition of albumin transcription also are not blocked by CHX, suggesting that these effects are primary consequences of GH-activated signal transduction pathways. By contrast, CHX completely inhibits the induction of activator protein-1 DNA-binding activity by GH, indicating that this action is secondary to the stimulation of Fos and/or Jun protein biosynthesis. Our results support the idea that multiple primary and secondary signaling pathways contribute to the pleiotropic effects of GH on gene expression and provide a framework for delineating the mechanisms controlling the acute actions of GH.

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