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.

Keywords:
Hypothalamic-pituitary-adrenal axis, CRF-41, Neural stimuli, Negative feedback, Glucocorticoids, Corticosteroid receptors
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© 1993 S. Karger AG, Basel
1993
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