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Peptides derived from pro-growth hormone-releasing hormone activate p38 mitogen-activated protein kinase in GH3 pituitary cells

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Abstract

Posttranslational processing of the pro-growth hormone-releasing hormone (proGHRH) peptide can result in the formation of at least two peptide products: GHRH and the C-terminal peptide, GHRH-related peptide (GHRH-Rp). While cyclic adenosine monophosphate transduces many of the actions of GHRH, other pathways also have been implicated in its actions. The aims of this study were to examine and characterize the activation of mitogen-activated protein kinase (MAPK) pathways by GHRH, and GHRH-RP in pituitary-derived GH3 cells, as well as the activation of the transcription factors that serve as substrates for these kinases. GHRH rapidly increased p44/p42 MAPK activity in GH3 cells in a protein kinase A-dependent and a protein kinase C-independent manner and stimulated the activation of the transcription factor Elk-1. By contrast, GHRH-RP, and p75-92NH2 had no effect on p44/p42 MAPK phosphorylation in these cells. Additionally, we determined that all three peptides, GHRH, GHRH-RP, and p75-92NH2, rapidly and specifically increase phosphorylation of p38 MAPK and stimulate the activation of the nuclear factor CHOP. These are the first studies to demonstrate the activation of Elk-1 by GHRH and the activation of p38 MAPK and CHOP by GHRH, GHRH-RP, and p75-92NH2. We conclude, that members of the GHRH family of peptides differentially activate multiple intracellular signaling pathways and suggest that the biologic actions of GHRH may be far more diverse than previously thought.

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Authors and Affiliations

  1. Section of Pediatric Endocrinology/Diabetology, Wells Center for Pediatric Research, Department of Pediatrics, Physiology and Biophysics, Indiana University School of Medicine, Room A5984, 702 Barnhill Drive, 46202, Indianapolis, IN

    Rosemary Steinmetz, Pingyu Zeng, Denise Walker King, Emily Walvoord & Ora Hirsch Pescovitz

  2. James Whitcomb Riley Hospital for Children, Room A5984, 702 Barnhill Drive, 46202, Indianapolis, IN

    Rosemary Steinmetz, Pingyu Zeng, Denise Walker King, Emily Walvoord & Ora Hirsch Pescovitz

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  1. Rosemary Steinmetz
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  2. Pingyu Zeng
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  4. Emily Walvoord
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  5. Ora Hirsch Pescovitz
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Correspondence to Rosemary Steinmetz.

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Steinmetz, R., Zeng, P., King, D.W. et al. Peptides derived from pro-growth hormone-releasing hormone activate p38 mitogen-activated protein kinase in GH3 pituitary cells. Endocr 15, 119–127 (2001). https://doi.org/10.1385/ENDO:15:1:119

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  • DOI: https://doi.org/10.1385/ENDO:15:1:119

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