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Am J Physiol Endocrinol Metab (February 3, 2009). doi:10.1152/ajpendo.90946.2008
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Submitted on November 26, 2008
Revised on January 15, 2009
Accepted on February 2, 2009

Diurnal Expression of Functional and Clock-Related Genes in the Rat Hypothalamus-Pituitary-Adrenal Axis. System-Wide shifts in Response to Restricted Feeding

Milena Girotti1*, Marc S Weinberg2, and Robert Spencer2

1 Univesity of Texas Health Science Center
2 University of Colorado

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

The diurnal rhythm of glucocorticoid secretion depends on the suprachiasmatic (SCN) and dorsomedial (putative food-entrainable oscillator; FEO) nuclei of the hypothalamus, two brain regions critical for coordination of physiological responses to photoperiod and feeding cues, respectively. In both cases, time keeping relies upon diurnal oscillations in clock gene (per 1, per 2, and bmal) expression. Glucocorticoids may play a key role in synchronization of the rest of the body to photoperiod and food availability. Thus, glucocorticoid secretion may be both a target and an important effector of SCN and FEO output. Remarkably little, however, is known about the functional diurnal rhythms of the individual components of the hypothalamic-pituitary-adrenal (HPA) axis. We examined the 24h pattern of hormonal secretion (ACTH and corticosterone), functional gene expression (c-fos, crh, pomc, star) and clock gene expression (per1, per2 and bmal) in each compartment of the HPA axis under a 12h light/dark cycle and in comparison to relevant SCN gene expression. We found that each anatomical component of the HPA axis has a unique circadian signature of functional and clock gene expression. We then tested the susceptibility of these measures to non-photic entrainment cues by restricting food availability to only a portion of the light phase of a 12h light/dark cycle. Restricted feeding is a strong zeitgeber that can dramatically alter functional and clock gene expression at all levels of the HPA axis, despite ongoing photoperiod cues and only minor changes in SCN clock gene expression. Thus the HPA axis may be an important mediator of the body entrainment to the FEO.







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