کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2012021 1067022 2010 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effects of neurosteroids on the human corticotropin-releasing hormone gene
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Effects of neurosteroids on the human corticotropin-releasing hormone gene
چکیده انگلیسی
Increased activity of hypothalamic-pituitary-adrenal (HPA) axis and hypersecretion of corticotropin-releasing hormone (CRH) are known to be important factors in pathogenesis of some stress-related diseases. Some neurosteroids exert anxiolytic and antidepressant effects probably by inhibition of HPA axis activity. The aim of our study was to find out if neurosteroids can directly affect human CRH gene transcription. The effect of allopregnanolone (ALLO), allotetrahydrodeoxycorticosterone (THDOC), pregnenolone (PGL), PGL sulfate (PGL-S), dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) on CRH expression was determined in differentiated Neuro-2A cells stably transfected with plasmid containing a fragment of human CRH promoter (-663 to + 124 bp) linked to the chloramphenicol acetyltransferase (CAT) reporter gene. It was found that PGL (0.3-30 μΜ), ALLO (1-30 μΜ) and THDOC (1-30 μΜ) present in the culture medium for 5 days in the concentration-dependent manner inhibited CRH-CAT activity. These neurosteroids also inhibited forskolin-stimulated CRH gene transcription with similar potency. In contrast, PGL-S, DHEA and DHEA-S in a concentration from 0.01 to 10 μΜ had no effect on basal and forskolin-stimulated CRH activity. Further experiments revealed that wortmannin (an inhibitor of phosphatidylinositol 3-kinase; PI3-K) at concentrations of 0.01 and 0.02 μΜ did not change the inhibitory effect of ALLO (3 μΜ) and PGL (1 μΜ) on CRH gene transcription. Moreover, ALLO (3 μΜ) and PGL (1 μΜ) present in the culture medium for 5 days did not change the amount of active, phosphorylated form of protein kinase B (PKB, Akt) and extracellular signal-regulated kinase (ERK). The obtained results indicate that PGL, ALLO and THDOC inhibited basal and forskolin-induced CRH gene promoter activity in the differentiated Neuro-2A cells and that these effects did not depend on the activation of PI3-K/Akt and ERK-MAPK pathways.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacological Reports - Volume 62, Issue 6, November–December 2010, Pages 1030-1040
نویسندگان
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