Glucocorticoids differentially increase nerve growth factor and basic fibroblast growth factor expression in the rat brain.
Adrenocorticotropin hormone (ACTH) and adrenal steroids may influence trophic processes operative in neuronal plasticity. Because nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) participate in neuronal trophism, we have investigated whether adrenal steroids induce the expression of these two trophic factors in the rat brain. The systemic administration of dexamethasone (DEX) elicited a rapid (within 3 hr) and sustained accumulation of bFGF and NGF mRNA in the cerebral cortex and hippocampus. Regional studies showed that DEX increases bFGF but not NGF mRNA in the cerebellum, striatum, and hypothalamus. In situ hybridization studies revealed that DEX increases NGF mRNA in superficial layers of the cerebral cortex and in the dentate gyrus of the hippocampus, and bFGF mRNA throughout the brain, suggesting that DEX induces NGF mRNA in neurons and bFGF in glial cells. ACTH administered systemically elicited a temporal and regional induction in NGF and bFGF mRNA similar to that obtained with DEX. Increases in NGF and bFGF mRNAs were also observed after administration of corticosterone and, albeit to a lesser extent, aldosterone, suggesting that the pituitary-adrenocortical axis plays an important role in the regulation of NGF and bFGF expression in the brain. Our data suggest that NGF and bFGF represent a link by which the adrenal cortical system can exert trophic action on the CNS.
Mocchetti
I
I
Department of Cell Biology, Division of Neurobiology, Georgetown University, School of Medicine, Washington, DC 20007, USA.
Spiga
G
G
Hayes
V Y
VY
Isackson
P J
PJ
Colangelo
A
A
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000737:chemistry / Q000502:physiology; D003345:Corticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000187:drug effects / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006624:Hippocampus / Q000737:chemistry / Q000502:physiology; D009414:Nerve Growth Factors / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D005938:Glucocorticoids; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D000450:Aldosterone; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone