کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8338005 | 1540985 | 2016 | 39 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cyp3a deficiency enhances androgen receptor activity and cholesterol synthesis in the mouse prostate
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کلمات کلیدی
PRKCDSHBGLDLRSREBP2HMGCRd-dopachrome tautomeraseCYP3ACytochrome P450 3ASBPSCAPHMGCS1SREBF2HMG-CoA reductase - HMG-CoA ردوکتازchromatin immunoprecipitation - ایمن سازی کروماتینtestosterone - تستوسترونDDT - دیکرو دیفنیل تری کلرواتانCytochrome P450 - سیتوکروم پی۴۵۰androgen response element - عنصر پاسخ آندروژنwild-type - نوع وحشیARE - هستندsrebp cleavage-activating protein - پروتئین فعال کننده پروتئین Srebpsterol regulatory element-binding protein 2 - پروتئین متصل کننده عصاره استرول 2Protein Kinase C Delta - پروتئین کیناز C دلتاProstate - پروستاتCHiP - چیپhigh-performance liquid chromatography - کروماتوگرافی مایعی کاراHPLC - کروماتوگرافی مایعی کاراcholesterol - کلسترولSex hormone-binding globulin - گلوبولین اتصال دهنده هورمون جنسیAndrogen Receptor - گیرنده آندروژنیlow density lipoprotein receptor - گیرنده لیپوپروتئین چگالی کم
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Cyp3a deficiency enhances androgen receptor activity and cholesterol synthesis in the mouse prostate Cyp3a deficiency enhances androgen receptor activity and cholesterol synthesis in the mouse prostate](/preview/png/8338005.png)
چکیده انگلیسی
Testosterone regulates cellular functions in the prostate through activation of the androgen receptor (AR), which may enhance expression levels of cholesterogenic enzymes through activation of sterol regulatory element-binding protein2 (SREBP2). Because testosterone is inactivated to 6β-hydroxytestosterone by cytochrome P450 3A (CYP3A), we examined the effects of Cyp3a deficiency on circulating testosterone levels and its effects on activation of the AR and expression levels of cholesterogenic enzymes in the prostate using Cyp3a-knockout (Cyp3aâ/â) mice. The results showed that Cyp3aâ/â mice had remarkably increased free testosterone levels in plasma along with suppressed testosterone 6β-hydroxylation activities in liver microsomes, suggesting that Cyp3a is a major determinant of systemic levels of testosterone in mice. The results also showed that mRNA expression levels of the AR target genes were increased significantly, and that AR bindings to the promoter region of the AR target genes were more abundant in the prostates of Cyp3aâ/â mice. These findings suggest that AR activation was stimulated in the prostate of Cyp3aâ/â mice. In addition, the protein expression levels of SREBP cleavage-activating protein (SCAP), mRNA expression levels of SREBP2 target genes and total cholesterol contents were increased in the prostates of Cyp3aâ/â mice. The findings suggest that Cyp3a deficiency stimulated the expression of Scap via activation of the AR, which elevated cholesterogenic gene expression levels through activation of SREBP2 and increased total cholesterol contents in the prostate.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 163, October 2016, Pages 121-128
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 163, October 2016, Pages 121-128
نویسندگان
Mari Hashimoto, Kaoru Kobayashi, Mana Yamazaki, Yasuhiro Kazuki, Shoko Takehara, Mitsuo Oshimura, Kan Chiba,