Somatotroph hypoplasia and dwarfism in transgenic mice expressing a non-phosphorylatable CREB mutant (original) (raw)

Nature volume 350, pages 622–624 (1991)Cite this article

Abstract

MOST of the transcriptional effects of cyclic AMP are mediated by the cAMP response element binding protein (CREB)1,2. After activation of cAMP-dependent protein kinase A, the catalytic subunits of this enzyme apparently mediate the phosphorylation and activation of CREB3,4. As cAMP serves as a mitogenic signal for anterior pituitary somatotrophic cells5, we investigated whether CREB similarly regulates proliferation of these cells.We prepared transgenic mice expressing a transcriptionally inactive mutant of CREB (CREBM1), which cannot be phosphorylated, in cells of the anterior pituitary. If CREB activity is required for proliferation, the overexpressed mutant protein would effectively compete with wild-type CREB activity and thereby block the response to cAMP. As predicted, the CREBM1 transgenic mice exhibited a dwarf phenotype with atrophied pituitary glands markedly deficient in somatotroph but not other cell types. We conclude that transcriptional activation of CREB is necessary for the normal development of a highly restricted cell type, and that environmental cues, possibly provided by the hypothalamic growth hormone-releasing factor, are necessary for population of the pituitary by somatotrophic cells.

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Authors and Affiliations

  1. The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California, 92037, USA
    R. Scott Struthers, Wylie W. Vale & Marc R. Montminy
  2. Laboratory of Neuronal Structure and Function, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California, 92037, USA
    Carlos Arias & Paul E. Sawchenko
  3. Graduate Program in Biomedical Science, University of California, San Diego, 9500 Oilman Drive, La Jolla, California, 92093-0636, USA
    R. Scott Struthers & Wylie W. Vale

Authors

  1. R. Scott Struthers
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  2. Wylie W. Vale
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  3. Carlos Arias
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  4. Paul E. Sawchenko
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  5. Marc R. Montminy
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Struthers, R., Vale, W., Arias, C. et al. Somatotroph hypoplasia and dwarfism in transgenic mice expressing a non-phosphorylatable CREB mutant.Nature 350, 622–624 (1991). https://doi.org/10.1038/350622a0

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