Effects of phenolic compounds on 3β-hydroxysteroid dehydrogenase activity in human and rat placenta: Screening, mode of action, and docking analysis.

doi:10.1016/j.jsbmb.2022.106202

科研成果详情

题名	Effects of phenolic compounds on 3β-hydroxysteroid dehydrogenase activity in human and rat placenta: Screening, mode of action, and docking analysis.
作者	Shi, Lei1; Meng, Fangyan2; Wang, Shaowei1; Hu, Zhiyan2; Li, Jingjing2; Tian, Fuhong2; Wang, Haixing2; Zhu, Yang 2; Wang, Yiyan2; Ge, Ren-shan1,2,3; Li, Huitao1,3
发表日期	2023-01
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 ; Research Support, Non-U.S. Gov't
关键词	3β-hydroxysteroid dehydrogenase 1 Endocrine disruptors Inhibition Phenolic compounds Pregnenolone Progesterone
其他关键词	TYPE-1 ; STRUCTURE/FUNCTION ; PROGESTERONE ; NONYLPHENOL ; EXPRESSION
摘要	Human 3β-hydroxysteroid dehydrogenase type I (HSD3B1) and rat type IV (HSD3B4) in placentas catalyze the conversion of pregnenolone to progesterone, which plays a key role in maintaining pregnancy. Many phenolic compounds potentially inhibit HSD3B in placentas as endocrine disruptors. In this study, the effects of 16 phenolic compounds on the activity of human HSD3B1 and rat HSD3B4 were determined and the structure-activity relationship was compared. HSD3B1 in human placental microsomes and HSD3B4 in rat placental microsomes were used to measure their activities and pregnenolone and NAD+ were used as substrates. Of the 16 phenolic compounds, 4-nonylphenol, pentabromophenol, and 2-bromophenol resulted in residual human HSD3B1 activity lower than 50 % and 4-nonylphenol and pentabromophenol resulted in residual rat HSD3B4 activity lower than 50 %. 4-Nonylphenol, pentabromophenol, and 2-bromophenol were mixed inhibitors of human HSD3B1, with Ki values of 2.31, 3.58 and 4.86 µM, respectively, while 4-nonylphenol and pentabromophenol were noncompetitive inhibitors of rat HSD3B4 with Ki values of 20.86 and 141.8 µM. Molecular docking showed that 4-nonylphenol, pentabromophenol, and 2-bromophenol docked to the active sites of human HSD3B1 and rat HSD3B4, and the shift of residue S125 in human HSD3B1 to T125 in rat HSD3B4 could explain the species-dependent difference in their inhibitory potency and mode of action. This study demonstrates that 4-nonylphenol, pentabromophenol, and 2-bromophenol are mixed inhibitors of human placental HSD3B1, while 4-nonylphenol and pentabromophenol are noncompetitive inhibitors of rat HSD3B4, possibly blocking the placental steroidogenesis
资助项目	Health and Family Planning Commission of Zhejiang Province; [11-CX29]
出版者	PERGAMON-ELSEVIER SCIENCE LTD
ISSN	0960-0760
EISSN	1879-1220
卷号	225 页码:106202
DOI	10.1016/j.jsbmb.2022.106202
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:000876979400004
收录类别	PUBMED ; SCIE ; SCOPUS
在线发表日期	2022-10
URL	查看原文
PubMed ID	36241036
SCOPUSEID	2-s2.0-85142400892
通讯作者地址	[Ge, Ren-shan]Department of Obstetrics and Gynecology,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325027,China
Scopus学科分类	Endocrinology, Diabetes and Metabolism;Biochemistry;Molecular Medicine;Molecular Biology;Endocrinology;Clinical Biochemistry;Cell Biology
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/166909
专题	第二临床医学院，附属第二医院、育英儿童医院
通讯作者	Ge, Ren-shan
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 Anaesthesiology,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325027,China; 3.Key Laboratory of Structural Malformations in Children of Zhejiang Province,Zhejiang Province,Wenzhou,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
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
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	Shi, Lei,Meng, Fangyan,Wang, Shaowei,et al. Effects of phenolic compounds on 3β-hydroxysteroid dehydrogenase activity in human and rat placenta: Screening, mode of action, and docking analysis.[J]. The Journal of steroid biochemistry and molecular biology,2023,225:106202.
APA	Shi, Lei., Meng, Fangyan., Wang, Shaowei., Hu, Zhiyan., Li, Jingjing., ... & Li, Huitao. (2023). Effects of phenolic compounds on 3β-hydroxysteroid dehydrogenase activity in human and rat placenta: Screening, mode of action, and docking analysis.. The Journal of steroid biochemistry and molecular biology, 225, 106202.
MLA	Shi, Lei,et al."Effects of phenolic compounds on 3β-hydroxysteroid dehydrogenase activity in human and rat placenta: Screening, mode of action, and docking analysis.".The Journal of steroid biochemistry and molecular biology 225(2023):106202.