title: Negative feedback regulation following administration of chronic exogenous corticosterone.
abstract: Administration of exogenous glucocorticoids is known to suppress the HPA axis and has been reported to occupy brain glucocorticoid receptors, eventually leading to down-regulation. To determine the effects of chronic corticosterone administration on HPA axis function, corticosterone was administered as both 25% and 50% corticosterone/cholesterol pellets. Rats were sacrificed 6 days after corticosterone pellet implantation. The 25% corticosterone pellets produced a small increase in morning corticosterone concentrations but no change in evening ACTH or corticosterone secretion. The 50% corticosterone pellets produced constant corticosterone concentrations of 5-6 micrograms/dl, with no circadian variation in corticosterone, indicating inhibition of evening ACTH and corticosterone secretion. The 25% corticosterone pellets produced no significant decrease in thymus weight or in adrenal weight; 50% corticosterone pellets produced significant decreases in thymus weight and adrenal weight. Neither 25% nor 50% corticosterone pellets produced significant decreases in GR in hippocampus and cortex. The 50% corticosterone pellets treatment resulted in a decrease in anterior pituitary POMC mRNA levels, a decrease in baseline and oCRH stimulated ACTH release from the anterior pituitary, and a near complete inhibition of the AM and PM response to restraint stress. These results suggest that: 1) the HPA axis was able to adjust to the small increase in glucocorticoids produced by the 25% cort pellets with minimal disturbances in function and 2) 50% corticosterone pellets exert a significant inhibitory effect on stress and diurnal ACTH secretion which appears to be exerted at the pituitary as well as possible inhibitory effects on brain.
authors.affiliation: Mental Health Research Institute, University of Michigan, Ann Arbor 48109, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Young
authors.forename: S P
authors.initials: SP
authors.lastname: Kwak
authors.forename: J
authors.initials: J
authors.lastname: Kottak
mesh_terms: D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D015415:Biomarkers; D003345:Corticosterone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004343:Drug Implants; D005246:Feedback / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000502:physiology
chemical_list: D015415:Biomarkers; D004343:Drug Implants; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone