Corticosterone infused intracerebroventricularly inhibits energy storage and stimulates the hypothalamo-pituitary axis in adrenalectomized rats drinking sucrose.
When allowed to drink sucrose, bilaterally adrenalectomized (ADX) rats exhibit normal weight gain, food intake, sympathetic neural activity, and ACTH compared with sham-ADX rats. Furthermore, ADX rats drinking sucrose have normal corticotropin-releasing factor (CRF) mRNA throughout brain. In ADX rats without sucrose, all of these variables are abnormal. Systemic corticosterone (B) replacement also restores these variables in ADX rats to normal. To test whether B acts centrally, we infused B or saline intracerebroventricularly into ADX rats under basal conditions and after repeated restraint. Rats were exposed to no stress or 3 h/d restraint for 3 d. Body weights and food and fluid intakes were measured. Brains were analyzed using immunocytochemistry against glucocorticoid receptors (GR) and CRF. Intracerebroventricular B blocked the positive effects of sucrose on metabolism, increased basal ACTH concentrations, and augmented ACTH responses to restraint on d 3. B-infused rats exhibited nuclear GR staining in perirhinal cortex, hippocampus, and hypothalamic paraventricular nuclei, showing that infused B spreads effectively. CRF staining in the paraventricular nucleus of the hypothalamus was higher in B- than in saline-infused rats. We conclude that under basal conditions B acts systemically, but not in the brain, to restore metabolism and neuropeptides after adrenalectomy. By contrast, tonic GR occupancy in brain initiates metabolic and ACTH responses characteristic of stress.
Laugero
Kevin D
KD
Department of Physiology and Program in Neuroscience, University of California, San Francisco, California 94143-0444, USA.
Gomez
Francisca
F
Manalo
Sotara
S
Dallman
Mary F
MF
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D001923:Brain Chemistry; D002552:Cerebral Ventricles / Q000187:drug effects; D003345:Corticosterone / Q000008:administration & dosage*; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D019422:Dietary Sucrose / Q000008:administration & dosage*; D004326:Drinking; D004734:Energy Metabolism / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000032:analysis; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000503:physiopathology
D001786:Blood Glucose; D019422:Dietary Sucrose; D007328:Insulin; D020738:Leptin; D011965:Receptors, Glucocorticoid; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone