کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1993023 1541079 2007 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Long-term exposure to dehydroepiandrosterone affects the transcriptional activity of the glucocorticoid receptor
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Long-term exposure to dehydroepiandrosterone affects the transcriptional activity of the glucocorticoid receptor
چکیده انگلیسی

Although the antiglucocorticoid 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 h 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 103, Issue 2, February 2007, Pages 129–136
نویسندگان
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