Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. STKE, 4 October 2005
Vol. 2005, Issue 304, p. pe48
[DOI: 10.1126/stke.3042005pe48]

PERSPECTIVES

Intracellular Glucocorticoid Signaling: A Formerly Simple System Turns Stochastic

George P. Chrousos1,2* and Tomoshige Kino2

1Department of Pediatrics, University of Athens, Athens 115 27, Greece.
2Pediatric Endocrinology Section, Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.

Summary: Glucocorticoids contribute fundamentally to the maintenance of basal and stress-related homeostasis in all higher organisms. The major roles of these steroids in physiology are amply matched by their remarkable contributions to pathology. Glucocorticoids influence about 20% of the expressed human genome, and their effects spare almost no organs or tissues. For many years we thought that the numerous actions of glucocorticoids were mediated by a single receptor molecule: the classic glucocorticoid receptor (GR) isoform {alpha}, a complex, multifunctional domain protein, operating as a ligand-dependent transcription factor. The GR gene, however, encodes two 3' splicing variants, GR{alpha} and GRß, from alternative use of two distinct terminal exons (9{alpha} and 9ß), and each variant mRNA is translated from at least eight initiation sites into multiple GR{alpha} and possibly GRß isoforms, amounting to a minimum of 16 GR monomers and 256 different homo- or heterodimers. The translational GR{alpha} isoforms may be produced variably in target tissues, have varying intrinsic transcriptional activities, and influence different complements of glucocorticoid-responsive genes. It is likely that expression and functional differences might also be present between the putative GRß translational isoforms. The presence of multiple GR monomers and dimers in different quantities with quantitatively and qualitatively different transcriptional activities suggests that the glucocorticoid signaling system is highly stochastic.

*Corresponding author. E-mail: chrousge{at}med.uoa.gr

Citation: G. P. Chrousos, T. Kino, Intracellular Glucocorticoid Signaling: A Formerly Simple System Turns Stochastic. Sci. STKE 2005, pe48 (2005).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Circadian rhythm transcription factor CLOCK regulates the transcriptional activity of the glucocorticoid receptor by acetylating its hinge region lysine cluster: potential physiological implications.
N. Nader, G. P. Chrousos, and T. Kino (2009)
FASEB J 23, 1572-1583
   Abstract »    Full Text »    PDF »
ATF2 impairs glucocorticoid receptor mediated transactivation in human CD8+ T cells.
L.-b. Li, D. Y. M. Leung, M. J. Strand, and E. Goleva (2007)
Blood 110, 1570-1577
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882