Chemicals of environmental concern as inhibitors of human placental 3β-hydroxysteroid dehydrogenase 1 and aromatase: Screening and docking analysis.

doi:10.1016/j.cbi.2022.110243

科研成果详情

题名	Chemicals of environmental concern as inhibitors of human placental 3β-hydroxysteroid dehydrogenase 1 and aromatase: Screening and docking analysis.
作者	Tang, Luming1,3; Shi, Lei 2,3; Tang, Yunbing2; Ying, Yingfen 2; Dong, Yaoyao 3; Li, Huitao1,2,3; Ge, Ren-Shan1,2,3
发表日期	2022-12-01
发表期刊	Chemico-biological interactions 影响因子和分区
语种	英语
原始文献类型	Article
关键词	3β-hydroxysteroid dehydrogenase 1 Aromatase Bisphenol A Bisphenol AF Diethylstilbestrol Zearalenone
其他关键词	(-)-GOSSYPOLS POTENTLY INHIBIT ; 3-BETA-HYDROXYSTEROID DEHYDROGENASE ; 17-BETA-HYDROXYSTEROID-DEHYDROGENASE 3 ; STRUCTURAL BASIS ; RISK-ASSESSMENT ; BISPHENOL-A ; ISOMERASE ; TYPE-1 ; DIETHYLSTILBESTROL ; KETOCONAZOLE
摘要	Many environmental pollutants act as endocrine-disrupting compounds by inhibiting human placental 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase type 1 (HSD3B1) and aromatase (CYP19A1) activities. In this study, we screened 13 chemicals of environmental concern for their ability to inhibit human HSD3B1 and CYP19A1 by measuring the conversion of pregnenolone to progesterone for HSD3B1 activity and the conversion of testosterone to 17β-estradiol for CYP19A1 activity in human JEG-3 choriocarcinoma cell microsomes. HSD3B1 had an apparent Km of 0.323 μM and an apparent Vmax of 0.111 nmol/mg/min and CYP19A1 had an apparent Km of 56 nM and an apparent Vmax of 0.177 nmol/mg protein/min. 17β-Estradiol, bisphenol A, and bisphenol AF competitively inhibited HSD3B1 with Ki values of 0.8, 284.1, and 141.2 μM, respectively, while diethylstilbestrol had a mixed inhibition on human HSD3B1 with the Ki of 8.0 μM. Ketoconazole, bisphenol A, and bisphenol AF noncompetitively inhibited CYP19A1 with Ki values of 10.3, 54.4, and 45.7 μM, respectively, while diethylstilbestrol and zearalenone competitively suppressed CYP19A1 with Ki values of 63.0 and 16.6 μM, respectively. Docking analysis showed that 17β-estradiol, diethylstilbestrol, bisphenol A, and bisphenol AF bound the steroid binding pocket facing the catalytic residues Y155 and K159 of HSD3B1, and that ketoconazole, bisphenol A, and bisphenol AF bound heme binding pocket while diethylstilbestrol and zearalenone bound the steroid binding site of CYP19A1. In conclusion, 17β-estradiol, diethylstilbestrol, bisphenol A, and bisphenol AF are human HSD3B1 inhibitors, and ketoconazole, zearalenone, diethylstilbestrol, bisphenol A, and bisphenol AF are human CYP19A1 inhibitors
资助项目	NSFC; [81730042]
出版者	ELSEVIER IRELAND LTD
出版地	CLARE
ISSN	0009-2797
EISSN	1872-7786
卷号	368 页码:110243
DOI	10.1016/j.cbi.2022.110243
页数	12
WOS类目	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
WOS记录号	WOS:000892562700001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	36374910
SCOPUSEID	2-s2.0-85141756826
通讯作者地址	[Ge, Ren-Shan]Department of Emergency Medicine,The Second Affiliated Hospital and Yuying Children Hospital of Wenzhou Medical University,Zhejiang,325000,China ; [Li, Huitao]Department of Emergency Medicine,The Second Affiliated Hospital and Yuying Children Hospital of Wenzhou Medical University,Zhejiang,325000,China
Scopus学科分类	Toxicology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/171430
专题	第一临床医学院（信息与工程学院）、附属第一医院_急诊医学
通讯作者	Li, Huitao; Ge, Ren-Shan
作者单位	1.Department of Emergency Medicine,The Second Affiliated Hospital and Yuying Children Hospital of Wenzhou Medical University,Zhejiang,325000,China; 2.Department of Obstetrics and Gynecology,The Second Affiliated Hospital and Yuying Children Hospital of Wenzhou Medical University,Zhejiang,325000,China; 3.Key Laboratory of Structural Malformations in Children of Zhejiang Province,Zhejiang Province,Wenzhou,325000,China
第一作者单位	第一临床医学院（信息与工程学院）、附属第一医院_急诊医学
通讯作者单位	第一临床医学院（信息与工程学院）、附属第一医院_急诊医学
第一作者的第一单位	第一临床医学院（信息与工程学院）、附属第一医院_急诊医学
推荐引用方式 GB/T 7714	Tang, Luming,Shi, Lei,Tang, Yunbing,et al. Chemicals of environmental concern as inhibitors of human placental 3β-hydroxysteroid dehydrogenase 1 and aromatase: Screening and docking analysis.[J]. Chemico-biological interactions,2022,368:110243.
APA	Tang, Luming., Shi, Lei., Tang, Yunbing., Ying, Yingfen., Dong, Yaoyao., ... & Ge, Ren-Shan. (2022). Chemicals of environmental concern as inhibitors of human placental 3β-hydroxysteroid dehydrogenase 1 and aromatase: Screening and docking analysis.. Chemico-biological interactions, 368, 110243.
MLA	Tang, Luming,et al."Chemicals of environmental concern as inhibitors of human placental 3β-hydroxysteroid dehydrogenase 1 and aromatase: Screening and docking analysis.".Chemico-biological interactions 368(2022):110243.