Glucocorticoid Feedback Regulation of Adrenocortical Responses to Neural Stimuli: Role of CRF-41 and Corticosteroid Type I and Type II Receptors

Publisher Website
Google Scholar
Abstract
In the present study we characterized the negative feedback effect of exogenous and endogenous glucocorticoids (GC) on the responses of the hypothalamo-pituitary-adrenal (HPA) axis to neural stimuli in male rats. Dexamethasone (Dex) was injected intraperitoneally at a dose of 0.5-4.0 µg/100 g BW and rats were exposed to photic or acoustic stress 3.5 h later. The serum ACTH and corticosterone (CS) responses to these stimuli were inhibited in a dose-dependent manner by Dex, such that the stress-induced response was completely abolished at a Dex dose of 4.0 µg/100 g BW. Injection of Dex (4.0 µg/100 g BW i.p.) did not affect the content of CRF-41 at the median eminence under basal conditions but prevented the depletion in CRF-41 content following acoustic and photic stimulation observed in vehicle-treated animals. Pretreatment with a subcutaneous injection of corticosteroid type I receptor antagonist RU-28318 (5 mg/100 g BW) did not affect the inhibition of the stress-induced adrenocortical response exerted by Dex; in contrast the type II receptor antagonist RU-38486 (5 mg/100 g BW) completely abolished the inhibitory effect of Dex following both types of neural stimuli. To investigate the role of type I and type II corticosteroid receptors in mediating the feedback effect of endogenous GC, the two receptor antagonists were injected intracerebroventriculary (100 ng/100 g BW). RU-28318 did not affect the response to photic stress at 10, 30 or 90 min following the stress, whereas RU-38486 caused a significant increase (∼40%) in serum ACTH and CS at all three time points tested. We conclude that the response of the HP A axis induced by neural stimuli is sensitive to inhibition by Dex, which is mediated by a reduction of CRF-41 release from the median eminence. In addition, the feedback effect exerted by exogenous or endogenous GC following neural stress appears to be mediated by type II GC receptors.

This publication has 0 references indexed in Scilit: