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Independent mechanisms of cyclic AMP and glucocorticoid action

Nature volume 268, pages 167–169 (1977)Cite this article

Abstract

IN eukaryotic cells, cyclic adenosine monophosphate (cyclic AMP) acts as the intracellular mediator for several hormones (for example, adrenaline and certain polypeptide hormones)1 and plays an important part in the modulation of cell proliferation2,3. This cyclic nucleotide is known to function by activating a protein kinase4,5 which mediates the phosphorylation of specific proteins, thereby modifying their biological activity. The activation of protein kinase may, in fact, be the sole mechanism of action of cyclic AMP in mammalian cells6,7. Glucocorticoids, and steroid hormones in general, act through a mechanism8,9 which involves the binding of the hormone to specific cytoplasmic receptor proteins, the translocation of the receptor–steroid complex into the cell nucleus and the association with chromatin. The cellular responses to glucocorticoids and cyclic AMP are quite similar in several systems and the potentiating effect of the steroid on cyclic AMP-mediated processes is often referred to as ‘permissive effect’ (for reviews see refs 10 and 11). In several cell types glucocorticoids have been reported to increase, although moderately, the intracellular concentration of cyclic AMP (refs 12–15). These observations suggest that the cyclic nucleotide and glucocorticoids could have some distal step(s) in common in their mechanism of action. We have tested this hypothesis by cloning responsive cells in the presence of both effectors and report here that resistance to cyclic AMP and glucocorticoids occurs independently.

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Authors and Affiliations

  1. Institut für Biologische Chemie der Universität Heidelberg, Im Neuenheimer Feld 501, 69, Heidelberg, Germany

    U. GEHRING

  2. Department of Microbiology, University of California, San Francisco, San Francisco, California, 94143

    P. COFFINO

Authors
  1. U. GEHRING
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  2. P. COFFINO
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GEHRING, U., COFFINO, P. Independent mechanisms of cyclic AMP and glucocorticoid action. Nature 268, 167–169 (1977). https://doi.org/10.1038/268167a0

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