Nature communicationsApr 7, 2026

A brain circuit controlling daily rhythms of stress hormone release

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 28, 2026

Abstract

Essence

In male mice, an SCN-to-SPZ-to-DMH hypothalamic circuit drives the circadian corticosterone surge before the active period.

Evidence

This preclinical circuit study in male mice showed that both glutamatergic and GABAergic DMH neurons regulate PVH-CRH neurons to produce the daily corticosteroid surge.

Caveat

The findings come from a mechanistic male-mouse model, so their relevance to female animals and humans is uncertain.

Simplified

There is a strong circadian rhythm of corticosteroid secretion in animals and humans, but the circuit for translating the suprachiasmatic (SCN) clock light-dark cycle rhythm into an increase in corticosteroid secretion beginning several hours before the active period is not known. We show here that in male mice, this rhythm depends upon input from the SCN to the subparaventricular zone (SPZ), and then to the dorsomedial nucleus of the hypothalamus (DMH). Both glutamatergic and GABAergic DMH neurons are required for the daily surge of corticosteroid secretion in anticipation of the active period. Glutamatergic DMH neurons directly excite paraventricular nucleus corticotrophin-releasing hormone (PVH-CRH) neurons, whereas DMH GABA neurons disinhibit PVH-CRH neurons via a relay in GABAergic neurons in the caudoventral PVH. This circuit underlies the daily surge in corticosteroid secretion that is temporally linked but phase advanced compared to the SCN activity cycle.