Signal transducer and activator of transcription (Stat) 5b-mediated inhibition of insulin-like growth factor binding protein-1 gene transcription: A mechanism for repression of gene expression by growth hormone

Mitsuru Ono, Dennis J. Chia, Roxana Merino-Martinez, Amilcar Flores-Morales, Terry G. Unterman, Peter Rotwein

    Research output: Contribution to journalArticlepeer-review

    29 Scopus citations

    Abstract

    GH plays a central role in controlling somatic growth, tissue regeneration, and intermediary metabolism in most vertebrate species through mechanisms dependent on the regulation of gene expression. Recent studies using transcript profiling have identified large cohorts of genes whose expression is induced by GH. Other results have demonstrated that signal transducer and activator of transcription (Stat) 5b, a latent transcription factor activated by the GH receptor-associated protein kinase, Jak2, is a key agent in the GH-stimulated gene activation that leads to somatic growth. By contrast, little is known about the steps through which GH-initiated signaling pathways reduce gene expression. Here we show that Stat5b plays a critical role in the GH-regulated inhibition of IGF binding protein-1 gene transcription by impairing the actions of the FoxO1 transcription factor on the IGF binding protein-1 promoter. Additional observations using transcript profiling in the liver indicate that Stat5b may be a general mediator of GH-initiated gene repression. Our results provide a model for understanding how GH may simultaneously stimulate and inhibit the expression of different cohorts of genes via the same transcription factor, potentially explaining how GH action leads to integrated biological responses in the whole organism.

    Original languageEnglish (US)
    Pages (from-to)1443-1457
    Number of pages15
    JournalMolecular Endocrinology
    Volume21
    Issue number6
    DOIs
    StatePublished - Jun 2007

    ASJC Scopus subject areas

    • Molecular Biology
    • Endocrinology

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