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Abstract
Feedback inhibition of the adrenocortical axis by circulating glucocorticoids occurs
at the pituitary and CNS sites. In the CNS, both hypothalamic and suprahypothalamic
sites have been implicated as mediators of glucocorticoid feedback activity. In the
present experiments, we have attempted to identify specific CNS regions mediating
the feedback and to characterize which hypothalamic adrenocorticotropic hormone secretagogues
are under glucocorticoid inhibitory control. Adrenalectomized rats were presented
with a delayed feedback signal in the form of systemic infusion with corticosterone
or dexamethasone. Hypophysial-portal concentrations of corticotropin-releasing factor
(CRF), arginine vasopressin (AVP), and oxytocin (OT) were determined before and during
a hypotensive stressor in the face of varying levels of feedback. The rats were then
killed, and the extent of total, type I, and type II corticosteroid receptor occupancy
in hippocampus, hypothalamus, and amygdala was determined. The following observations
were made: (1) increased hippocampal corticosteroid receptor occupancy was associated
with suppressed adrenocorticotropic hormone secretagogue concentrations; (2) the major,
significant predictor of initial (prehypotensive) concentrations of CRF, AVP, and
OT was the extent of occupancy of hippocampal type II receptors, often in combination
with occupancy of hippocampal type I or hypothalamic receptors; (3) secretion of CRF
induced by hypotension was best predicted by hippocampal type I and type II receptor
occupancy (stress-induced OT secretion was best predicted by hippocampal type II and
hypothalamic receptor occupancy), and (4) the ‘shape’ of the hippocampal type II receptor
occupancy versus initial AVP concentration curve suggested a nonlinear, threshold
type of relationship, implying tight hippocampal regulation of AVP secretion.