The importance of the circadian trough in glucocorticoid signaling: a variation on B-flat

Abstract

Glucocorticoid hormones are essential for health, but overexposure may lead to many detrimental effects, including metabolic, psychiatric, and bone disease. These effects may not only be due to increased overall exposure to glucocorticoids, but also to elevated hormone levels at the time of the physiological circadian trough of glucocorticoid levels. The late Mary Dallman developed a model that allows the differentiation between the effects of overall 24-hour glucocorticoid overexposure and the effects of a lack of circadian rhythmicity. For this, she continuously treated rats with a low dose of corticosterone (or “B”), which leads to a constant hormone level, without 24-hour overexposure using subcutaneously implanted pellets. The data from this “B-flat” model suggest that even modest elevations of glucocorticoid signaling during the time of the normal circadian trough of hormone secretion are a substantial contributor to the negative effects of glucocorticoids on health.

Keywords:

• Stress
• HPA-Axis
• glucocorticoid receptor
• mineralocorticoid receptor
• osteoporosis
• hippocampus
• metabolic disease

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

O.C.M. receives funding from Corcept Therapeutics, who develop glucocorticoid receptor modulators for clinical use.