Journal
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
Volume 103, Issue 2, Pages 129-136Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2006.08.003
Keywords
DHEA; dexamethasone; glucocorticoid receptor; TUBO cells; nuclear translocation; EMSA
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Although the antightcocorticoid effects of dehydroepiandrosterone (DHEA) have been demonstrated in vivo in many systems, controversial results have been reported by in vitro studies. In order to elucidate the long-term antiglucocorticoid effects of DHEA in vitro in a context more physiological than what proposed by previous works, we set up a system consisting of a carcinoma cell line relying on endogenously produced glucocorticoid receptor (GR) and stably expressing a reporter gene ErbB-2 under the control of a GR-dependent MMTV promoter. These cells grown in presence of low levels of serum glucocorticoids (GC) showed a basal translocation and activity of endogenous GR. The cells reacted to high concentrations of dexamethasone increasing GR nuclear import, although down-regulating receptor expression, and enhancing GR-dependent transcriptional activity, as shown by EMSA assay and expression of the reporter gene ErbB-2. The response to GC was also functional since the increase of ErbB-2 boosted cellular growth. On the contrary, 72 It of incubation with DHEA diminished basal GR-dependent reporter expression and abated cellular proliferation. Analysing molecular mechanisms responsible for this failed transcriptional activity, upon prolonged treatment with DHEA we observed a slow nuclear import of GR not followed by its recruitment to DNA. These data add novel information about the long-term effects of DHEA in vitro. (c) 2006 Elsevier Ltd. All rights reserved.
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