{"title":"PFOA affects androgen metabolism","authors":"Louise Lloyd","doi":"10.1038/s41585-024-00985-6","DOIUrl":null,"url":null,"abstract":"<p>A novel, endocrine-disrupting property of the perfluoroalkyl substance perfluorooctanoic acid (PFOA) affecting androgen metabolism has been discovered. This discovery has implications for our understanding of the effect of PFOA on the actions of androgens.</p><p>In spectrofluorimetric inhibitor screens and inhibition studies, PFOA was identified to potently, competitively and specifically inhibit aldo-keto reductase 1C2 (AKR1C2), which catalyses the reduction of 5α-dihydrotestosterone (5α-DHT) to the inactive steroid 3α-androstanediol, in the nanomolar range. This property was found to be a result of valine being present in the binding pocket. Thus, PFOA inhibited the reduction of 5α-DHT, resulting in its accumulation. Androgen receptor transactivation was increased by PFOA-induced blocking of 5α-DHT metabolism owing to inhibition of AKR1C2.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"220 1","pages":""},"PeriodicalIF":12.1000,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Reviews Urology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41585-024-00985-6","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
A novel, endocrine-disrupting property of the perfluoroalkyl substance perfluorooctanoic acid (PFOA) affecting androgen metabolism has been discovered. This discovery has implications for our understanding of the effect of PFOA on the actions of androgens.
In spectrofluorimetric inhibitor screens and inhibition studies, PFOA was identified to potently, competitively and specifically inhibit aldo-keto reductase 1C2 (AKR1C2), which catalyses the reduction of 5α-dihydrotestosterone (5α-DHT) to the inactive steroid 3α-androstanediol, in the nanomolar range. This property was found to be a result of valine being present in the binding pocket. Thus, PFOA inhibited the reduction of 5α-DHT, resulting in its accumulation. Androgen receptor transactivation was increased by PFOA-induced blocking of 5α-DHT metabolism owing to inhibition of AKR1C2.
期刊介绍：
Nature Reviews Urology is part of the Nature Reviews portfolio of journals.Nature Reviews' basic, translational and clinical content is written by internationally renowned basic and clinical academics and researchers. This journal targeted readers in the biological and medical sciences, from the postgraduate level upwards, aiming to be accessible to professionals in any biological or medical discipline.
The journal features authoritative In-depth Reviews providing up-to-date information on topics within a field's history and development. Perspectives, News & Views articles, and the Research Highlights section offer topical discussions and opinions, filtering primary research from various medical journals.
Covering a wide range of subjects, including andrology, urologic oncology, and imaging, Nature Reviews provides valuable insights for practitioners, researchers, and academics within urology and related fields.
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