کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2131182 | 1086626 | 2009 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Regulation of steroid 5-α reductase type 2 (Srd5a2) by sterol regulatory element binding proteins and statin
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کلمات کلیدی
qPCRSREBP-2LDLRSRD5A2SREBPHmg3-hydroxy-3-methylglutaryl - 3-هیدروکسی-3-متیل گلوتاریلQuantitative PCR - PCR کمیStatin - استاتینchromatin immunoprecipitation - ایمن سازی کروماتینAndrogen regulation - تنظیم آندروژنTranscription regulation - مقررات رونویسیsterol regulatory element binding protein - پروتئین اتصال دهنده عصاره استرولCHiP - چیپlow density lipoprotein receptor - گیرنده لیپوپروتئین چگالی کم
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
In this study, we show that sterol regulatory element binding proteins (SREBPs) regulate expression of Srd5a2, an enzyme that catalyzes the irreversible conversion of testosterone to dihydroxytestosterone in the male reproductive tract and is highly expressed in androgen-sensitive tissues such as the prostate and skin. We show that Srd5a2 is induced in livers and prostate from mice fed a chow diet supplemented with lovastatin plus ezitimibe (L/E), which increases the activity of nuclear SREBP-2. The three fold increase in Srd5a2 mRNA mediated by L/E treatment was accompanied by the induction of SREBP-2 binding to the Srd5a2 promoter detected by a ChIP-chip assay in liver. We identified a SREBP-2 responsive region within the first 300 upstream bases of the mouse Srd5a2 promoter by co-transfection assays which contain a site that bound SREBP-2 in vitro by an EMSA. Srd5a2 protein was also induced in cells over-expressing SREBP-2 in culture. The induction of Srd5a2 through SREBP-2 provides a mechanistic explanation for why even though statin therapy is effective in reducing cholesterol levels in treating hypercholesterolemia it does not compromise androgen production in clinical studies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 315, Issue 18, 1 November 2009, Pages 3133-3139
Journal: Experimental Cell Research - Volume 315, Issue 18, 1 November 2009, Pages 3133-3139
نویسندگان
Young-Kyo Seo, Bing Zhu, Tae-Il Jeon, Timothy F. Osborne,