Diurnal variation in resting levels of corticosterone is not mediated by variation in adrenal responsiveness to adrenocorticotropin but involves splanchnic nerve integrity.

Abstract

To study possible mechanisms controlling diurnal changes in corticosterone (CORT) levels, we tested the CORT responses to ACTH in the morning (AM) and evening (PM) in male Wistar and Sprague-Dawley rats. Rat ACTH-(1-39) or human ACTH-(1-24) (3.75-15 ng/rat) was given as an iv bolus or an intraarterial infusion to (un)anesthetized rats treated with dexamethasone (0.1-0.5 mg/kg, 2-6 h before ACTH). In all conditions studied, no AM/PM differences in CORT responses were found when ACTH was given in vehicle (pH 4.3-7). This contrasts with earlier studies in which ACTH was given in a strongly acid vehicle (pH 1-1.9). Administration of ACTH in such acid vehicle confirmed the reported AM/PM differences in CORT responses (P < 0.05). Because alterations in splanchnic nerve activity can modulate ACTH-induced CORT secretion, we studied the effect of splanchnic nerve transection (SPLNX) on the diurnal change in resting CORT levels in unilaterally adrenalectomized rats. SPLNX reduced resting CORT concentrations in the PM (approximately 50%; P < 0.05), but not in the AM. SPLNX did not abolish the acid vehicle-associated AM/PM differences in CORT responses to ACTH. We conclude that 1) diurnal variation in adrenal responsiveness to ACTH per se does not exist in this rat model; 2) the strongly acid vehicle interacts with ACTH-induced CORT secretion; 3) the PM rise in plasma CORT depends on the integrity of the sympathetic neural input to the adrenal gland.

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

“…Jasper and Engeland (1994) showed that denervation of the adrenal gland by removal of its sympathetic innervation resulted in increased secretory activity of the adrenal cortex during the daytime, thus supporting our suggestion for an important daytime inhibition of corticosterone release via the neural input to the adrenal gland. Recently, Dijkstra et al (1996) also showed that the sympathetic innervation of the adrenal gland contributes to the diurnal variation in resting plasma corticosterone levels. However, evidence also was provided that this is not attributable to a change in the adrenal responsiveness to ACTH.…”

Exercise-Associated Changes in the Corticosterone Response to Acute Restraint Stress: Evidence for Increased Adrenal Sensitivity and Reduced Corticosterone Response Duration

“…Prior to ACTH challenge, blood was sampled at 0800 hours to establish a baseline level of CORT. Mice were then given an injection of dexamethasone (0.05 mg/kg) in order to limit endogenous ACTH release (Dijkstra et al, 1996;Han et al, 1998;Michopoulos et al, 2012;Otsuka et al, 2012). This dose of dexamethasone was chosen as it exhibited equivalent CORT suppression in both groups following peripheral administration in Experiment 2.…”

Adrenal peripheral clock controls the autonomous circadian rhythm of glucocorticoid by causing rhythmic steroid production

“…However, there is still conflicting evidence on the issue of the daily alterations in adrenal responsiveness and accompanying HPA axis reactivity. For instance, it has been argued that the diurnal changes in GC require splanchnic nerve integrity but are not mediated by differential responsiveness to ACTH (12). It has also been shown that the response to a mild stress failed to support increased HPA axis reactivity during the active period (13).…”