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Development of a Liquid Chromatography/Mass Spectrometry-Based Inhibition Assay for the Screening of Steroid 5-α Reductase in Human and Fish Cell Lines.
Kim, Dahye; Cho, Hyunki; Eggers, Ruth; Kim, Sang Kyum; Ryu, Chang Seon; Kim, Young Jun.
Afiliação
  • Kim D; Environmental Safety Group, Korea Institute of Science and Technology (KIST) Europe Forschungsgesellschaft mbH, 66123 Saarbruecken, Germany.
  • Cho H; Environmental Safety Group, Korea Institute of Science and Technology (KIST) Europe Forschungsgesellschaft mbH, 66123 Saarbruecken, Germany.
  • Eggers R; Environmental Safety Group, Korea Institute of Science and Technology (KIST) Europe Forschungsgesellschaft mbH, 66123 Saarbruecken, Germany.
  • Kim SK; College of Pharmacy, Chungnam National University, Daejeon 34134, Korea.
  • Ryu CS; Environmental Safety Group, Korea Institute of Science and Technology (KIST) Europe Forschungsgesellschaft mbH, 66123 Saarbruecken, Germany.
  • Kim YJ; Environmental Safety Group, Korea Institute of Science and Technology (KIST) Europe Forschungsgesellschaft mbH, 66123 Saarbruecken, Germany.
Molecules ; 26(4)2021 Feb 08.
Article em En | MEDLINE | ID: mdl-33567691
Steroid 5-α reductase (5AR) is responsible for the reduction of steroids to 5-α reduced metabolites, such as the reduction of testosterone to 5-α dihydrotestosterone (DHT). A new adverse outcome pathway (AOP) for 5AR inhibition to reduce female reproduction in fish (AOP 289) is under development to clarify the antiestrogenic effects of 5AR inhibitors in female fish. A sensitive method for the DHT analysis using chemical derivatization and liquid chromatography-tandem mass spectrometry was developed. A cell-based 5AR inhibition assay that utilizes human cell lines, a transient overexpression system, and fish cell lines was developed. The measured IC50 values of two well-known 5AR inhibitors, finasteride and dutasteride, were comparable in the different systems. However, the IC50 of dutasteride in the fish cell lines was lower than that in the human cell lines. Finasteride showed a higher IC50 against the RTG-2 cell line. These results demonstrated that 5ARs inhibition could differ in terms of structural characteristics among species. The assay has high sensitivity and reproducibility and is suitable for the application in 5AR inhibition screening for various endocrine disruption chemicals (EDCs). Future studies will continue to evaluate the quantitative inhibition of 5AR by EDCs to compare the endocrine-disrupting pathway in different species.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Espectrometria de Massas / 3-Oxo-5-alfa-Esteroide 4-Desidrogenase / Cromatografia Líquida / Avaliação Pré-Clínica de Medicamentos / Inibidores de 5-alfa Redutase Tipo de estudo: Diagnostic_studies / Screening_studies Limite: Animals / Humans Idioma: En Revista: Molecules Assunto da revista: BIOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Espectrometria de Massas / 3-Oxo-5-alfa-Esteroide 4-Desidrogenase / Cromatografia Líquida / Avaliação Pré-Clínica de Medicamentos / Inibidores de 5-alfa Redutase Tipo de estudo: Diagnostic_studies / Screening_studies Limite: Animals / Humans Idioma: En Revista: Molecules Assunto da revista: BIOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Alemanha