Dose-dependent effects of corticosterone on nuclear glucocorticoid receptors and their binding to DNA in the brain and pituitary of the rat.
The glucocorticoid receptor (GR) is a transcription factor which regulates glucocorticoid-mediated negative feed-back of the HPA axis. In this study, we have investigated the dose-dependent effects of corticosterone on nuclear GR and GR-DNA binding in the brain and pituitary of adult adrenalectomized male rats. Rats were injected with either saline (1 ml/kg, i.p.) or corticosterone (0.1, 0.3, and 1 mg/kg, i.p.). Nuclear GR and GR-DNA binding were measured in nuclear extracts from hippocampus, hypothalamus, prefrontal cortex, amygdala and pituitary using Western immunoblotting and ELISA, respectively. We found that the dose-dependent effects of corticosterone on nuclear GR and GR-DNA binding are similar across all the areas we analyzed, although at lower levels of corticosterone changes were observed only in the hippocampus. These data have important implications for our understanding of tissue specificity of glucocorticoid action including the corticosteroid-mediated negative feed-back response of the HPA axis.
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK. F.Spiga@bristol.ac.uk
Francesca
F
Spiga
Stafford L
SL
Lightman
D000315:Adrenalectomy; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D003345:Corticosterone / Q000008:administration & dosage* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013347:Subcellular Fractions
D011965:Receptors, Glucocorticoid; D003345:Corticosterone