Diurnal-stimulated and stress-induced ACTH release in rats is mediated by ventral noradrenergic bundle

Abstract

Female rats were bilaterally injected with 3 micrograms of 6-hydroxydopamine (6-OHDA) dissolved in 0.2 microliter saline, via a glass micropipet stereotaxically implanted into the ventral noradrenergic-ascending bundle (VNAB). This bundle conveys most of the catecholaminergic innervation to the paraventricular nuclei and originates from the locus coeruleus and from two medullary groups of neurons (A1 and A2). Two weeks after injection, and 1 wk after the subsequent implantation of an arterial cannula, serial blood samples were taken from each rat over a 36-h period for assay of basal secretion patterns of ACTH and corticosterone (C) by radioimmunoassay and radiocompetition, respectively. Other blood samples were collected at short intervals over a 2-h period to explore the stress-ether responses of both hormones. Effects of 6-OHDA injections on catecholaminergic innervation were attested by the striking decrease in the histofluorescence of hypothalamic catecholamines and by the 86% drop in the hypothalamic noradrenaline concentrations measured by high-performance liquid chromatography at constant dopamine titers. Compared with control, sham-lesioned rats, pharmacological destruction of the VNAB by 6-OHDA led to 1) obliteration of the circadian patterns for ACTH and C and the emergence in their place of ultradian fluctuations of reduced amplitude above base-line levels and 2) 80% inhibition of the ACTH stress response which correlated with a short-lived, depressed C response. These results are discussed within the framework of the controversial literature on the mechanisms by which catecholamines may control corticotropic function.

Insulin-induced hypoglycemia stimulates corticotropin-releasing factor and arginine vasopressin secretion into hypophysial portal blood of conscious, unrestrained rams.

“…These observations suggest that the IIH-induced CRF and AVP release into HPB is mediated through extrahypothalamic pathways. We and others have shown recently that central catecholamines, originating from the brainstem nuclei, have a stimulatory effect on hypothalamic CRF secretion in the rat (27,28). Interestingly, hypothalamic norepinephrine activity is increased during IIH in rats, and this increase parallels the variation in plasma corticosterone (29).…”

Hyporesponsiveness of the Pituitary to CRH during Slow Wave Sleep Is Not Mimicked by Systemic GHRH

“…Mechanisms through which the HPA system may be restrained during sleep include activation of the mineralocorticoid-receptor [6]and reduced electrical activity of noradrenergic brainstem nuclei [3]. The latter could, by removing noradrenaline-mediated facilitation of ACTH release [35], contribute to the blunted response to intravenous CRH and at the same time favor α 2 -receptor-mediated GHRH release [1]. In contrast, intravenous administration of GHRH will act primarily at the pituitary level, leaving afferent pathways unaffected.…”

Induction and habituation of immediate early gene expression in rat brain by acute and repeated restraint stress

“…Morgan and Curran,199 l), in brain regions known to influence basal and stress-induced activity of this axis including the cortex, hippocampus, hypothalamus, septum, amygdala, and brainstem. Lesion and electrical stimulation studies have indicated that certain brainstem (Szafarczyk et al, 1985;Sawchenko, 199 1) and hypothalamic (Dohanics et al, 1986;Richardson-Morton et al, 1989) nuclei positively influence basal and stress-induced activity of the PA-axis. In contrast, specific cortical regions, hippocampus, and the lateral septal area are involved in inhibitory regulation of this axis (Seggie et al, 1973;Sapolsky et al, 1984;Saphier and Feldman, 1987;Herman et al, 1990).…”