Completed Diabetes, Hormones & Metabolism Brain & Nervous System

Pattern Dependent Specificity of Glucocorticoid Signalling

In plain English

AI plain-English summary

The body's stress hormones don't just rise and fall—they pulse in rapid, rhythmic bursts throughout the day, and this research tests whether those specific patterns, not just the total amount of hormone, determine how tissues like the brain and liver respond. Most studies treat stress hormones as a steady signal, but the body releases them in ultradian pulses (every 1–2 hours) on top of a daily circadian rhythm. This project asks whether cells "read" these digital-like patterns to decide which genes to switch on or off. The researchers will use an automated blood sampling and infusion system to deliver precise, programmable hormone rhythms to rats, then measure how different brain regions and the liver react—both in gene activity and in cognitive and metabolic outcomes. They will also disrupt the natural rhythm to see what breaks. This is fundamental science about how biological signals encode information. If the pattern—not just the dose—matters, it could reshape how doctors prescribe steroids for inflammation, autoimmune disease, or mental health conditions, moving from daily pills to timed, pulsatile delivery. It might also explain why shift work or chronic stress, which scramble these rhythms, damages memory and metabolism.

View original technical description
The specific hypothesis we plan to test is that the response to corticosteroids depends on a tissue s ability to read the digital signals from fluctuating glucocorticoid levels, by mechanisms involving interaction of the episodically activated corticosteroid receptors GR and MR with DNA and the basal transcriptional machinery. In order to test this hypothesis we aim: 1. To characterise the response of different cell groups within the brain and the liver to different patterns of circulating glucocorticoids. 2. To characterise how chronic alteration of the endogenous ultradian and diurnal pattern of glucocorticoid secretion will affect both cognitive and metabolic functions. These studies will utilise our automated blood sampling facility and also our newly developed automated infusion system which allows us to deliver - in vivo - any required pattern of ultradian and circadian rhythmicity of glucocorticoids that is experimentally required.

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Researchers

Stafford Lightman (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Next generation approaches to understand tissue specific regulation of the glucocorticoid response
The regulation of circadian and ultradian rhythmicity of circulating glucocorticoid hormones and their role in the optimisation of limbic activity
Studies on the distinct control of free corticosterone levels in the brain
The regulation of circadian and ultradian rhythmicity of circulating glucocorticoid hormones and their roles in the optimisation of limbic activity
Elucidating clock control of glucocorticoid action

Original classification

Programme Grant

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