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This version published online on February 15, 2007
Endocrinology, doi:10.1210/en.2006-1304
A more recent version of this article appeared on May 1, 2007
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Submitted on September 22, 2006
Accepted on February 2, 2007

Differential responses of HPA axis immediate early genes to corticosterone and circadian drive

Milena Girotti*, Marc S. Weinberg, and Robert L. Spencer

Division of Behavioral Neuroscience, Department of Psychology, University of Colorado, UCB 345, Boulder CO 80309, USA

* To whom correspondence should be addressed. E-mail: girotti{at}colorado.edu.

The hypothalamus-pituitary-adrenal (HPA) axis diurnal cycle of activity is manifest in circadian rhythms of ACTH and corticosterone secretion, which in the rat peak around the onset of the dark period. This cycle is thought to be driven by daily fluctuations in activity of CRH neurons within the paraventricular nucleus of the hypothalamus (PVN), controlled by suprachiasmatic nucleus inputs. In this study we examined whether the circadian drive that regulates ACTH and corticosterone basal secretion in the rat is reflected in PVN immediate early gene expression, and if so, whether different genes respond uniformly or uniquely to circadian stimulatory input. In addition, we examined how circadian drive and acute stress, two categories of stimuli that induce HPA axis activation, comparatively affect gene expression within different components of the HPA axis (c-fos mRNA, CRH hnRNA and zif268 mRNA in PVN; c-fos mRNA, POMC hnRNA and zif268 mRNA in anterior pituitary; c-fos mRNA and NGFI-B mRNA in adrenal cortex). Finally, we examined whether circadian differences in gene expression depend on endogenous glucocorticoids, and if so, whether the dependence is on an acute or permissive influence of the hormone. We found that a circadian drive that regulates HPA axis basal hormone secretion is also manifest on basal c-fos gene expression in the PVN. Moreover, we show that different immediate early genes within the HPA axis anatomical components display different diurnal patterns of gene expression. These differential patterns result, in part, from gene-specific responses to circadian signals and to acute and/or permissive glucocorticoid actions.


Key words: Immediate early genes • glucocorticoids • circadian rhythms • stress • HPA axis




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[Abstract] [Full Text] [PDF]




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