Delayed effects of chronic cortisol treatment on brain and plasma concentrations of corticotropin (ACTH) and beta-endorphin.
The effects of 2-day and 7-day cortisol treatment on immunoreactive corticotropin (ACTH) and beta-endorphin concentrations were measured in the cerebral cortex, hippocampus, hypothalamus, and cerebellum in male rats. Plasma ACTH, beta-endorphin, corticosterone, and cortisol levels were also measured in parallel. Cortisol administration by osmotic minipumps (25 mg/kg/day) maintained a constant, moderately high concentration (23.0 +/- 2.7 micrograms/100 ml) of this glucocorticoid in plasma. Two-day cortisol treatment suppressed the plasma concentration of ACTH and corticosterone, and also decreased, to a lesser degree, concentrations of beta-endorphin. ACTH and beta-endorphin levels in the brain remained unchanged after 2 days of cortisol treatment. After 7-day treatment, however, plasma concentrations of ACTH and beta-endorphin further decreased, while ACTH and beta-endorphin concentrations in the cortex and beta-endorphin concentrations in the cerebellum were also significantly decreased. Peptide concentrations in other brain areas did not change significantly with either 2-day or 7-day cortisol treatment. These data suggest that there are delayed effects of glucocorticoids on pro-opiomelanocortin peptide secretion and/or metabolism in the central nervous system. These findings are consistent with the impaired cognitive functions of patients with diseases, such as Cushing's syndrome and depression, that have long-lasting elevated cortisol secretion.
Bagdy
G
G
Section on Clinical Neuropharmacology, National Institute of Mental Health, Bethesda, MD 20892.
Calogero
A E
AE
Chrousos
G P
GP
Szemeredi
K
K
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004723:Endorphins / Q000097:blood*; D006854:Hydrocortisone / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D004723:Endorphins; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone