Lack of dexamethasone modulation of mRNAs involved in the glucocorticoid signal transduction pathway in two cell systems.
Glucocorticoids are final effectors of the stress response. These hormones exert negative feedback action at multiple levels of the hypothalamic-pituitary-adrenal axis and regulate a large number of central nervous system and peripheral target genes. The inactive form of the glucocorticoid receptor in the cytoplasm appears to be bound to heat shock proteins of the 90K family (hsp90 alpha and hsp90 beta). This interaction facilitates binding of glucocorticoid to its receptor and, therefore, its activation. The chicken ovalbumin upstream promoter transcription factor (COUP-TF) binds on a negative glucocorticoid response element in the 5' regulatory region of the proopiomelanocortin gene and prevents the repressive effect of glucocorticoids on this gene. The aim of this study was to examine the effect of glucocorticoids on the steady-state mRNAs of their own receptor, the two hsp90s, and COUP-TF. Quantitative Northern blot analysis in primary leukocytes and Epstein-Barr virus-transformed human lymphocytes (EBV-THL) basally and after a 24-hour exposure to 50 nM dexamethasone was performed. Treatment of primary leukocytes or normally growing EBV-THL with dexamethasone had no effect on the mRNA level of glucocorticoid receptor, hsp90 alpha, hsp90 beta, or COUP-TF. Similar treatment of EBV-THL grown in charcoal-stripped media, resulted in minimal changes in the mRNAs of these factors. Our findings suggest that glucocorticoids do not regulate the steady-state mRNA levels of these core components of the mammalian stress response in human primary and Epstein-Barr virus-transformed lymphocytes.
D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000235:genetics; D015342:DNA Probes; D004251:DNA Transposable Elements / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D004587:Electrophoresis, Agar Gel; D005938:Glucocorticoids / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D015342:DNA Probes; D004251:DNA Transposable Elements; D005938:Glucocorticoids; D012333:RNA, Messenger; D012313:RNA; D003907:Dexamethasone