Stress and glucocorticoid receptor transcriptional programming in time and space: Implications for the brain–gut axis

Dec 23, 2015Neurogastroenterology and motility

How Stress and Hormone Receptors Affect Gene Activity Over Time and Location, with Possible Effects on Brain and Gut Communication

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Cortisol may disrupt gene expression rhythms linked to stress-related disorders.

Chronic psychological stress is associated with increased abdominal pain and impaired intestinal barrier function.
The hypothalamic-pituitary-adrenal (HPA) axis plays a role in the stress response by regulating cortisol and corticosterone release.
Cortisol binds to the glucocorticoid receptor (GR) and influences gene expression in a tissue-specific manner.
Cortisol drives transcriptional activity in the CLOCK and PER gene families, with potential disruptions observed in major depressive disorder and related conditions.
Emerging evidence suggests that epigenetic regulation may affect how GR interacts with chromatin to control target gene expression.

AI simplified

BACKGROUND: Chronic psychological stress is associated with enhanced abdominal pain and altered intestinal barrier function that may result from a perturbation in the hypothalamic-pituitary-adrenal (HPA) axis. The glucocorticoid receptor (GR) exploits diverse mechanisms to activate or suppress congeneric gene expression, with regulatory variation associated with stress-related disorders in psychiatry and gastroenterology.

PURPOSE: During acute and chronic stress, corticotropin-releasing hormone drives secretion of adrenocorticotropic hormone from the pituitary, ultimately leading to the release of cortisol (human) and corticosterone (rodent) from the adrenal glands. Cortisol binds with the GR in the cytosol, translocates to the nucleus, and activates the NR3C1 (nuclear receptor subfamily 3, group C, member 1 [GR]) gene. This review focuses on the rapidly developing observations that cortisol is responsible for driving circadian and ultradian bursts of transcriptional activity in the CLOCK (clock circadian regulator) and PER (period circadian clock 1) gene families, and this rhythm is disrupted in major depressive disorder, bipolar disorder, and stress-related gastrointestinal and immune disorders. Glucocorticoid receptor regulates different sets of transcripts in a tissue-specific manner, through pulsatile waves of gene expression that includes occupancy of glucocorticoid response elements located within constitutively open spatial domains in chromatin. Emerging evidence supports a potentially pivotal role for epigenetic regulation of how GR interacts with other chromatin regulators to control the expression of its target genes. Dysregulation of the central and peripheral GR regulome has potentially significant consequences for stress-related disorders affecting the brain-gut axis.

Full Text

Full text is available at the source.

View full text ↗

Stress and glucocorticoid receptor transcriptional programming in time and space: Implications for the brain–gut axis

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief