A hypothalamic circuit for circadian regulation of corticosterone secretion

Apr 7, 2026Nature communications

A brain circuit controlling daily rhythms of stress hormone release

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

In male mice, the daily surge of corticosteroid secretion is regulated by a neural circuit involving the suprachiasmatic nucleus and the dorsomedial hypothalamus.

Corticosteroid secretion exhibits a strong circadian rhythm, starting several hours before the active period.
Input from the suprachiasmatic nucleus to the subparaventricular zone is crucial for this rhythm.
Both glutamatergic and GABAergic neurons in the dorsomedial nucleus of the hypothalamus are necessary for the corticosteroid surge.
Glutamatergic neurons directly stimulate corticotrophin-releasing hormone neurons in the paraventricular nucleus.
GABAergic neurons in the dorsomedial hypothalamus disinhibit these corticotrophin-releasing hormone neurons through another set of GABAergic neurons.

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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.