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Glucocorticoid Signaling pp 3–31Cite as

Regulatory Actions of Glucocorticoid Hormones: From Organisms to Mechanisms

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 872))

Abstract

The history of glucocorticoid hormone research is an excellent example of “bedside to bench” investigation. It started with two very insightful clinical observations. Thomas Addison described the syndrome of what came to be known as adrenal hormone insufficiency and Harvey Cushing the syndrome of glucocorticoid hormone excess. These dramatic and life-threatening conditions spawned 150 years of active research that has involved many disciplines; indeed some of the fundamental observations of molecular biology are the result of this work. We have a fundamental knowledge of how glucocorticoids regulate gene transcription, their major effect. The challenge facing current and future investigators is to discern how to use this information to make these powerful therapeutic agents safer and more effective.

Dedication 

We dedicate this chapter to Gordon M. Tomkins. Gordon was a visionary who, after direct exposure to the Paris bacterial genetics group in the early 1960s, quite clearly foresaw the field of mammalian gene regulation. He was one of the founders of the discipline now known as Molecular Endocrinology. Most importantly, as regards the topic of this book, his scientific passion was glucocorticoid action. A generation of young scientists was fortunate to spend time in his laboratory; many others were influenced by his writings, entertaining lectures and the informal talks he gave during his many visits to universities and research institutes. Gordon was a direct mentor to two of us, D.K.G. and K.R.Y., and a second generation mentor to J.-C.W.

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Notes

  1. 1.

    This effect helps explain an observation made more than 50 years ago. Wolf et al. showed that, in vitamin A deficient rats, hepatic cholesterol and fatty acid synthesis, the citric acid cycle, glycogen metabolism and glycolysis were all normal. Gluconeogenesis, however, was markedly impaired [104].

  2. 2.

    The GC accessory factor elements in the PEPCK gene promoter were originally referred to as AF1-3. As the designation of the transactivation domains in nuclear receptors became known as AF1 and AF2, the DNA elements in the PEPCK gene were designated gAF1-3.

  3. 3.

    All the experiments described in this section were performed using this cell line, which was derived from a rat hepatoma [42].

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Acknowledgements

The authors wish to thank Ms. Stacie Vik and Allison McQueen for their assistance in preparing the manuscript and Michael Stallcup for his incisive comments and encouragement during its preparation. We thank the many people who, over the years, performed experiments in our laboratories. All of their contributions could not be discussed, but all are a part of this story. We also are grateful to the legion of colleagues who, over years of their own work, and in formal and informal discussions, made our participation in this field so interesting.

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Authors and Affiliations

  1. Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, 169 Newton Road, 4312 PBDB, Iowa City, IA, 52242, USA

    Daryl K. Granner M.D.

  2. Department Internal Medicine, Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, 169 Newton Road, 4312 PBDB, Iowa City, IA, 52242, USA

    Daryl K. Granner M.D.

  3. Vanderbilt University School of Medicine, Nashville, TN, USA

    Daryl K. Granner M.D.

  4. Department of Nutritional Sciences and Toxicology, University of California Berkeley, 119 Morgan Hall, Berkeley, CA, 94720-3104, USA

    Jen-Chywan Wang Ph.D.

  5. Cellular & Molecular Pharmacology, University of California, San Francisco, 600 16th Street, Genentech Hall S572D, Campus Box 2280, San Francisco, CA, 94143-2280, USA

    Keith R. Yamamoto Ph.D.

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  1. Daryl K. Granner M.D.
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  2. Jen-Chywan Wang Ph.D.
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Correspondence to Daryl K. Granner M.D. .

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Editors and Affiliations

  1. Department of Nutritional Science & Toxicology, University of California Berkeley, Berkeley, California, USA

    Jen-Chywan Wang

  2. Division of Endocrinology Metabolism & Lipid Research, Department of Internal Medicine, Washington University School of Medicine Division of Endocrinology, St. Louis, Missouri, USA

    Charles Harris

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Granner, D.K., Wang, JC., Yamamoto, K.R. (2015). Regulatory Actions of Glucocorticoid Hormones: From Organisms to Mechanisms. In: Wang, JC., Harris, C. (eds) Glucocorticoid Signaling. Advances in Experimental Medicine and Biology, vol 872. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2895-8_1

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