Stress-induced glucocorticoids suppress the antisense molecular regulation of FGF-2 expression.
Psychological stress can upregulate basic fibroblast growth factor (FGF-2) expression. Because glucocorticoids can also upregulate FGF-2 expression, the present studies investigated whether stress-induced glucocorticoids mediate the effects of stress on FGF-2. FGF-2 is regulated by an FGF-2 antisense (AS) molecular mechanism and so the present experiments also, for the first time, assessed the effects of stress on FGF-2-AS mRNA, as well as the mediating role of glucocorticoids. The effects of either escapable shock (ES) or yoked-inescapable tail shock (IS) on FGF-2 and FGF-2-AS were determined. To test whether glucocorticoids mediate the effect of stress on FGF-2 and FGF-2-AS, animals were pretreated with temporary corticosterone (CORT) synthesis inhibitors and exposed to IS. To test whether glucocorticoids are sufficient to modulate FGF-2 and FGF-2-AS mRNA, animals were injected with CORT and mRNA measured. ES and IS similarly downregulated FGF-2-AS mRNA at 0 h post-stress and upregulated FGF-2 mRNA 2 h post-stress. Inhibition of CORT synthesis abrogated the effect of IS on both FGF-2-AS and FGF-2 mRNA. Exogenous CORT mimicked the effects of ES and IS on FGF-2, but not FGF-2-AS mRNA. The present study demonstrates that glucocorticoids mediate the effects of stress on FGF-2 and FGF-2-AS.
Frank
Matthew G
MG
Department of Psychology and Center for Neuroscience, Campus Box 345, University of Colorado, Boulder, CO 80309-0345, USA. matt.frank@colorado.edu
Der-Avakian
Andre
A
Bland
Sondra T
ST
Watkins
Linda R
LR
Maier
Steven F
SF
D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016372:RNA, Antisense / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000378:metabolism*; D013997:Time Factors
D005938:Glucocorticoids; D016372:RNA, Antisense; D016222:Fibroblast Growth Factor 2; D003345:Corticosterone