Diurnal Corticosterone Presence and Phase Modulate Clock Gene Expression in the Male Rat Prefrontal Cortex

Endocrinology. 2016 Apr;157(4):1522-34. doi: 10.1210/en.2015-1884. Epub 2016 Feb 22.


Mood disorders are associated with dysregulation of prefrontal cortex (PFC) function, circadian rhythms, and diurnal glucocorticoid (corticosterone [CORT]) circulation. Entrainment of clock gene expression in some peripheral tissues depends on CORT. In this study, we characterized over the course of the day the mRNA expression pattern of the core clock genes Per1, Per2, and Bmal1 in the male rat PFC and suprachiasmatic nucleus (SCN) under different diurnal CORT conditions. In experiment 1, rats were left adrenal-intact (sham) or were adrenalectomized (ADX) followed by 10 daily antiphasic (opposite time of day of the endogenous CORT peak) ip injections of either vehicle or 2.5 mg/kg CORT. In experiment 2, all rats received ADX surgery followed by 13 daily injections of vehicle or CORT either antiphasic or in-phase with the endogenous CORT peak. In sham rats clock gene mRNA levels displayed a diurnal pattern of expression in the PFC and the SCN, but the phase differed between the 2 structures. ADX substantially altered clock gene expression patterns in the PFC. This alteration was normalized by in-phase CORT treatment, whereas antiphasic CORT treatment appears to have eliminated a diurnal pattern (Per1 and Bmal1) or dampened/inverted its phase (Per2). There was very little effect of CORT condition on clock gene expression in the SCN. These experiments suggest that an important component of glucocorticoid circadian physiology entails CORT regulation of the molecular clock in the PFC. Consequently, they also point to a possible mechanism that contributes to PFC disrupted function in disorders associated with abnormal CORT circulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ARNTL Transcription Factors / genetics*
  • Adrenalectomy
  • Animals
  • Circadian Rhythm*
  • Corticosterone / metabolism*
  • Corticosterone / pharmacology
  • Gene Expression Profiling
  • In Situ Hybridization
  • Male
  • Period Circadian Proteins / genetics*
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism*
  • Rats, Sprague-Dawley
  • Suprachiasmatic Nucleus / drug effects
  • Suprachiasmatic Nucleus / metabolism


  • ARNTL Transcription Factors
  • Arntl protein, rat
  • Per1 protein, rat
  • Per2 protein, rat
  • Period Circadian Proteins
  • Corticosterone