Effects of organochlorine pesticides on human and rat 17β-hydroxysteroid dehydrogenase 1 activity: Structure-activity relationship and in silico docking analysis

doi:10.1016/j.jsbmb.2024.106510

科研成果详情

题名	Effects of organochlorine pesticides on human and rat 17β-hydroxysteroid dehydrogenase 1 activity: Structure-activity relationship and in silico docking analysis
作者	Gong, Chaochao 1,2,3,4; Chen, Sailing1; Tang, Yunbing1; Chen, Huiqian1; Xie, Jianghuan1; Lv, Yanning1; Shen, Zhefan1; Zhu, Yang 1,2,3,4; Wang, Shaowei1; Ge, Ren-shan1,2,3,4,5; Zhao, Junzhao1
发表日期	2024-06
发表期刊	The Journal of steroid biochemistry and molecular biology 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	17β-HSD1 BeWo cells Docking analysis Estradiol Organochlorine pesticides
其他关键词	HUMAN ESTROGENIC 17-BETA-HYDROXYSTEROID-DEHYDROGENASE ; DEHYDROGENASE ; SPECIFICITY ; INHIBITION ; ENDOSULFAN ; RESIDUES ; RECEPTOR ; NADP(+)
摘要	The objective of this study was to examine the effect of 11 organochlorine pesticides on human and rat 17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) in human placental and rat ovarian microsome and on estradiol production in BeWo cells. The results showed that the IC50 values for endosulfan, fenhexamid, chlordecone, and rhothane on human 17β-HSD1 were 21.37, 73.25, 92.80, and 117.69 μM. Kinetic analysis revealed that endosulfan acts as a competitive inhibitor, fenhexamid as a mixed/competitive inhibitor, chlordecone and rhothane as a mixed/uncompetitive inhibitor. In BeWo cells, all insecticides except endosulfan significantly decreased estradiol production at 100 μM. For rats, the IC50 values for dimethomorph, fenhexamid, and chlordecone were 11.98, 36.92, and 109.14 μM. Dimethomorph acts as a mixed inhibitor, while fenhexamid acts as a mixed/competitive inhibitor. Docking analysis revealed that endosulfan and fenhexamid bind to the steroid-binding site of human 17β-HSD1. On the other hand, chlordecone and rhothane binds to a different site other than the steroid and NADPH-binding site. Dimethomorph binds to the steroid/NADPH binding site, and fenhexamid binds to the steroid binding site of rat 17β-HSD1. Bivariate correlation analysis showed a positive correlation between IC50 values and LogP for human 17β-HSD1, while a slight negative correlation was observed between IC50 values and the number of HBA. ADMET analysis provided insights into the toxicokinetics and toxicity of organochlorine pesticides. In conclusion, this study identified the inhibitory effects of 3-4 organochlorine pesticides and binding mechanisms on human and rat 17β-HSD1, as well as their impact on hormone production
资助项目	Department of Health of Zhejiang Province[11-CX29];
出版者	PERGAMON-ELSEVIER SCIENCE LTD
ISSN	0960-0760
EISSN	1879-1220
卷号	240
DOI	10.1016/j.jsbmb.2024.106510
页数	11
WOS类目	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS研究方向	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS记录号	WOS:001216253800001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	38508472
SCOPUSEID	2-s2.0-85188538793
通讯作者地址	[Zhao, Junzhao]Department of Obstetrics and Gynecology,the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325027,China ; [Ge, Ren-shan]Department of Anesthesiology and Perioperative Medicine,the Second Affiliated Hospital and Yuying Children's Hospital,Key Laboratory of Pediatric Anesthesiology,Ministry of Education,Zhejiang,Wenzhou,325000,China
Scopus学科分类	Endocrinology, Diabetes and Metabolism;Biochemistry;Molecular Medicine;Molecular Biology;Endocrinology;Clinical Biochemistry;Cell Biology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/210333
专题	第二临床医学院、附属第二医院、育英儿童医院附属第二医院_麻醉重点学科实验室
通讯作者	Ge, Ren-shan; Zhao, Junzhao
作者单位	1.Department of Obstetrics and Gynecology,the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325027,China; 2.Department of Anesthesiology and Perioperative Medicine,the Second Affiliated Hospital and Yuying Children's Hospital,Zhejiang,Wenzhou,325027,China; 3.Key Laboratory of Pediatric Anesthesiology,Ministry of Education,Zhejiang,Wenzhou,325027,China; 4.Key Laboratory of Anesthesiology of Zhejiang Province,Wenzhou Medical University,Zhejiang,Wenzhou,325027,China; 5.Key Laboratory of Male Health and Environment of Wenzhou,Zhejiang Province,325000,China
第一作者单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院; 妇产科; 温州医科大学
通讯作者单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院; 妇产科
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院
推荐引用方式 GB/T 7714	Gong, Chaochao,Chen, Sailing,Tang, Yunbing,et al. Effects of organochlorine pesticides on human and rat 17β-hydroxysteroid dehydrogenase 1 activity: Structure-activity relationship and in silico docking analysis[J]. The Journal of steroid biochemistry and molecular biology,2024,240.
APA	Gong, Chaochao., Chen, Sailing., Tang, Yunbing., Chen, Huiqian., Xie, Jianghuan., ... & Zhao, Junzhao. (2024). Effects of organochlorine pesticides on human and rat 17β-hydroxysteroid dehydrogenase 1 activity: Structure-activity relationship and in silico docking analysis. The Journal of steroid biochemistry and molecular biology, 240.
MLA	Gong, Chaochao,et al."Effects of organochlorine pesticides on human and rat 17β-hydroxysteroid dehydrogenase 1 activity: Structure-activity relationship and in silico docking analysis".The Journal of steroid biochemistry and molecular biology 240(2024).