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学科主题临床医学
Direct androgen regulation of PDE5 gene or the lack thereof
Lin, C-S1; Xin, Z.2; Namiki, M.3; Albersen, M.4; Muller, D.5; Lue, T. F.1
关键词androgen erectile dysfunction PDE5 penis
刊名INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH
2013-05-01
DOI10.1038/ijir.2013.11
25期:3页:81-85
收录类别SCI
文章类型Review
WOS标题词Science & Technology
类目[WOS]Urology & Nephrology
资助者National Institutes of Health ; National Institutes of Health
研究领域[WOS]Urology & Nephrology
关键词[WOS]MUSCLE CONTRACTILE PATHWAYS ; ERECTILE DYSFUNCTION ; SMOOTH-MUSCLE ; CORPUS CAVERNOSUM ; PHOSPHODIESTERASE TYPE-5 ; CORPORA CAVERNOSA ; VENTRAL PROSTATE ; HUMAN MYOMETRIUM ; TESTOSTERONE ; RAT
英文摘要

Inhibition of phosphodiesterase-5 (PDE5) is a well-known mechanism for the effective treatment of erectile dysfunction (ED). Androgen supplementation has also been prescribed for treating ED. However, it has been widely accepted that androgen can upregulate PDE5 expression, and thus creating a paradox in which a positive regulator of erectile function (androgen) could possibly increase the level of a negative regulator (PDE5). To solve this paradox, we conducted a systematic search of the PubMed and a non-systematic search of the Internet using PDE5, erectile, penis, testosterone and androgen as keywords. The retrieved papers were analyzed for data concerning the expression and regulation of PDE5 by androgens. Human and rat PDE5A gene sequences were retrieved from GenBank and computer-analyzed. The results showed that a putative androgen-response element (ARE) was reported in a study of human PDE5A gene promoter, and this prompted a separate study on whether androgen regulates PDE5 expression. The positive outcome in the latter study has since been cited in 17 review and editorial articles as the underlying mechanism for androgen′s therapeutic effects on ED. In addition, five other research studies also reached the same conclusion. On the other hand, two independent studies on the genome-wide searches for androgen-regulated genes did not find PDE5A as a candidate. Sequence analysis conducted in this study also failed to find ARE in rat PDE5A gene. Two independent studies on Leydig cells also failed to find positive regulation of PDE5 expression by androgen. Two other studies found concomitant reduction of cavernous smooth muscle and PDE5 expression in castrated rats. One of these studies also found no effect of androgen on PDE5 expression in cultured cavernous smooth muscle cells. Thus, it appears that reduced PDE5 expression in castrated animals is due to reduced smooth muscle content and that PDE5A gene is not directly regulated by androgens.

语种英语
所属项目编号DK045370 ; DK64538 ; DK069655
资助者National Institutes of Health ; National Institutes of Health
WOS记录号WOS:000318965200001
Citation statistics
Cited Times:9[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62649
Collection北京大学第一临床医学院_男科中心
作者单位1.Univ Hosp Leuven, Dept Urol, Louvain, Belgium
2.Peking Univ, Hosp 1, Androl Ctr, Beijing 100871, Peoples R China
3.Univ Calif San Francisco, Sch Med, Dept Urol, Knuppe Mol Urol Lab, San Francisco, CA 94143 USA
4.Kanazawa Univ, Grad Sch Med Sci, Dept Integrat Canc Therapy & Urol, Kanazawa, Ishikawa, Japan
5.Univ Giessen, Inst Anat & Cell Biol, D-35390 Giessen, Germany
Recommended Citation
GB/T 7714
Lin, C-S,Xin, Z.,Namiki, M.,et al. Direct androgen regulation of PDE5 gene or the lack thereof[J]. INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH,2013,25(3):81-85.
APA Lin, C-S,Xin, Z.,Namiki, M.,Albersen, M.,Muller, D.,&Lue, T. F..(2013).Direct androgen regulation of PDE5 gene or the lack thereof.INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH,25(3),81-85.
MLA Lin, C-S,et al."Direct androgen regulation of PDE5 gene or the lack thereof".INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH 25.3(2013):81-85.
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