Work

Clocks on steroids: how glucocorticoid receptors tell cells the time

Year: 2026

Type: article

Abstract: Glucocorticoid (GC) steroid hormone signalling via the glucocorticoid receptor (GR) underlies most daily physiological rhythms in mammals by synchronising cellular circadian rhythms throughout the body. Impaired circadian synchrony is associated with many non-communicable diseases, such as cardiovascular disease, diabetes and cancer. The functions and daily regulation of systemic GC levels are relatively well understood, yet a clearly defined mechanism for GC/GR-mediated circadian synchronisation is lacking. Historically, mechanistic studies of GR action have focused on its role as a transcription factor, sufficient to explain many, but not all, consequences of GC/GR signalling. Recently, several non-canonical modes of GR action have been described and proposed as a basis for understanding rapid cellular responses to GCs that cannot be explained by relatively slow changes in transcription. Here, we review the current state of knowledge on the cellular mechanism of GR signalling in the context of GR-mediated circadian synchronisation, outline gaps in current understanding and suggest new avenues for investigation.

Source: Journal of Endocrinology

DOI: 10.1530/joe-25-0340

Authors: Anna Edmondson, Joseph Menzies, David W Ray, John S O’Neill

Language: English

Topic: Circadian rhythm and melatonin

Subfield: Endocrine and Autonomic Systems

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funders: UK Research and Innovation, National Institute for Health and Care Research, Medical Research Council

Award: G94917711