Autoregulation of glucocorticoid receptor by cortisol in rainbow trout hepatocytes.
Sathiyaa, Ramesh, and Mathilakath M. Vijayan.
Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1,
Canada
APStracts 10:0057C, 2003.
We used primary cultures of trout hepatocytes and a physiological dose of cortisol (100
ng/ml), mimicking stressed levels in salmonid fish, to address the impact of
glucocorticoid stimulation on glucocorticoid receptor (GR) mRNA abundance and
protein content. Cortisol significantly elevated GR mRNA content over a 24-h period;
this increase was abolished by actinomycin D, suggesting transcriptional control of GR.
However, cortisol significantly decreased GR protein content, leading us to hypothesize
that lower GR protein content may be regulating GR mRNA abundance. Indeed,
treatment of hepatocytes with MG-132, a proteasomal inhibitor shown to prevent GR
degradation by cortisol, abolished cortisol-mediated GR mRNA upregulation. Also,
geldanamycin, a heat shock protein 90-specific inhibitor, abolished the GR mRNA
increase evident with cortisol but did not modify cortisol-induced increases in abundance
of mRNA for phosphoenolpyruvate carboxykinase, a glucocorticoid-responsive gene, or
hepatocyte glucose release. Together, our results suggest a negative feedback loop for GR
gene regulation by cortisol in trout hepatocytes. The autoregulation of GR may be a
crucial step in the physiological stress response process, especially in modulating energy-
dependent processes that are glucocorticoid dependent, including gluconeogenesis.
Received 28 September 2002; accepted in final form 3 February 2003
APS Manuscript Number C448-2.
Article publication pending Am J Physiol Cell Physiol
ISSN 1080-4757 Copyright 2003 The American Physiological Society.
Published in APStracts on 25 March 2003