Glucocorticoid feedback regulation of adrenocortical responses to neural stimuli: role of CRF-41 and corticosteroid type I and type II receptors.
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 micrograms/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 micrograms/100 g BW. Injection of Dex (4.0 micrograms/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 intracerebroventricularly (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 (approximately 40%) in serum ACTH and CS at all three time points tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Weidenfeld
J
J
Department of Neurology, Hadassah University Hospital, Jerusalem, Israel.
Feldman
S
S
D000161:Acoustic Stimulation; D000302:Adrenal Cortex / Q000502:physiology*; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology*; D005246:Feedback; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D010775:Photic Stimulation; D051381:Rats; D011919:Rats, Inbred Strains; D011987:Receptors, Steroid / Q000502:physiology*
D011987:Receptors, Steroid; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone