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Insulin regulation of growth hormone receptor gene expression: involvement of both the PI-3 kinase and MEK/ERK signaling pathways

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Abstract

The mechanism(s) of insulin’s effects on growth hormone receptor (GHR) gene expression are poorly understood. Using rat hepatoma cells, we have previously shown that insulin treatment reduces GHR mRNA and protein in a time- and concentration-dependent manner, at least in part via down-regulation of GHR transcription. The present study determines whether the phosphatidylinositol-3 kinase (PI-3 kinase) and mitogen activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways are involved in mediating these effects of insulin. Inhibition of the PI-3 kinase pathway partially blocked insulin’s reduction of GHR mRNA, as did inhibition of the MEK/ERK pathway, resulting in higher GHR mRNA levels. Inhibition of both pathways was necessary to completely block insulin effects. Similar results were obtained for GHR protein. Collectively, these data suggest that insulin signaling via either the PI-3 kinase or MEK/ERK pathway may result in partial reduction of GHR gene expression, whereas signaling via both pathways may be required to achieve the full insulin effect.

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Abbreviations

ERK:

Extracellular signal-regulated kinase

GH:

Growth hormone

GHR:

Growth hormone receptor

MEK:

Mitogen activated protein kinase kinase

PI-3 kinase:

Phosphatidylinositol-3 kinase

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Acknowledgments

We would like to thank Drs. Stuart Frank, Yuchen Ma, Adam B. Keeton, LaWanda T. Holland, Jie Xu, and John Lee Franklin for their helpful and insightful discussions and suggestions. This work was supported by grants from the National Institutes of Health (DK40456 and DK62071), the DOD (W81XWH-0510387) and the Veterans Administration Merit Review to Joseph L. Messina.

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Authors and Affiliations

  1. Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama at Birmingham, Volker Hall, G019, 1670 University Blvd, Birmingham, AL, 35294-0019, USA

    William L. Bennett, Adam B. Keeton, Shaonin Ji, Jie Xu & Joseph L. Messina

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  1. William L. Bennett
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  2. Adam B. Keeton
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  3. Shaonin Ji
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Correspondence to Joseph L. Messina.

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Bennett, W.L., Keeton, A.B., Ji, S. et al. Insulin regulation of growth hormone receptor gene expression: involvement of both the PI-3 kinase and MEK/ERK signaling pathways. Endocr 32, 219–226 (2007). https://doi.org/10.1007/s12020-007-9021-2

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  • DOI: https://doi.org/10.1007/s12020-007-9021-2

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