Further evidence for the central effect of dexamethasone at the hypothalamic level in the negative feedback mechanism.
The site of action of glucocorticoids (GC) in exerting negative feedback upon the hypothalamo-pituitary-adrenocortical (HPA) axis is not yet clear. In the present study we have examined whether dexamethasone (Dex) can inhibit the HPA axis stress responses by acting locally at the hypothalamic level in freely moving male rats. Local micro-injection of Dex in the paraventricular nuclei (PVN; 1 microg) prevented a decrease of CRH-41 content in the median eminence. The PVN Dex injections (0.25-1 microg) also inhibited the rise in plasma ACTH and corticosterone (CS) following short photic stimulation in a dose dependent manner. In PVN Dex-injected rats, i.v. injection of CRH-41 increased serum ACTH and CS levels similar to that observed in rats injected with saline into the PVN indicating normal sensitivity of the pituitary gland to CRH-41. Local injection of [3H]Dex in the PVN showed that only a negligible amount of radioactivity was found in the pituitary. These data indicate that minute amounts of Dex in the PVN, which did not affect the pituitary, blocked the HPA axis responses to photic stimulation. It is suggested that Dex may exert its inhibitory effect on the HPA axis at least in part at the hypothalamic level.
Feldman
Shaul
S
Department of Neurology, The Agnes Ginges Center for Neurogenetics, Hadassah University Hospital and Hebrew University-Hadassah Medical School, POB 12000, Jerusalem 91120, Israel. ovadia@hadassah.org.il
Weidenfeld
Joseph
J
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D025461:Feedback, Physiological / Q000187:drug effects* / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D010775:Photic Stimulation / Q000379:methods; D051381:Rats
D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone