A Diurnal Rhythm of Stimulatory Input to the Hypothalamo–Pituitary–Adrenal System as Revealed by Timed Intrahypothalamic Administration of the Vasopressin V₁Antagonist

TLDR

The suprachiasmatic nuclei act as an endogenous pacemaker that drives daily rhythms in behavior and hormone secretion. The study aimed to test whether the SCN imposes its circadian rhythm on the rest of the brain through rhythmic release of its transmitters in target areas. Microdialysis‑mediated intracerebral delivery of a vasopressin V1‑receptor antagonist was used to probe the mechanisms controlling basal corticosterone release. Timed antagonist administration uncovered a second, stimulatory SCN input to the HPA axis that peaks in the late light period 4–6 h after the vasopressin peak, and together with the known inhibitory input, these opposing circadian signals precisely time the corticosterone peak.

Abstract

The mammalian suprachiasmatic nuclei (SCN) contain an endogenous pacemaker that generates daily rhythms in behavior and secretion of hormones. We hypothesized that the SCN imposes its circadian rhythm on the rest of the brain via a rhythmic release of its transmitters in its target areas. Previously, we demonstrated a pronounced inhibitory effect of vasopressin (VP), released from SCN terminals in the dorsomedial hypothalamus, on the release of the adrenal hormone corticosterone. In the present study, microdialysis-mediated intracerebral administration of the VP V 1 -receptor antagonist was used to pursue the study of the mechanisms underlying the circadian control of basal corticosterone release. Using timed administrations of the VP antagonist divided equally over the day/night cycle, we were able to uncover the existence of an additional stimulatory input from the SCN to the hypothalamo–pituitary–adrenal (HPA) axis. Peak activity of this stimulatory SCN input takes place during the second half of the light period, after the daily peak of VP secretion, with a delay of ∼4–6 hr. In all likelihood, the inhibitory and stimulatory circadian input via separate mechanisms affects corticosterone release. Together, these two opposing circadian control mechanisms of the HPA axis enable a precise timing of the circadian peak in corticosterone release.