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

被引:6
|
作者
Shi, Lei [1 ,2 ]
Meng, Fangyan [3 ,4 ]
Wang, Shaowei [1 ,2 ]
Hu, Zhiyan [3 ,4 ]
Li, Jingjing [3 ,4 ]
Tian, Fuhong [3 ,4 ]
Wang, Haixing [3 ,4 ]
Zhu, Yang [3 ,4 ]
Wang, Yiyan [3 ,4 ]
Ge, Ren-shan [1 ,2 ,3 ,4 ,5 ]
Li, Huitao [1 ,2 ,5 ]
机构
[1] Wenzhou Med Univ, Dept Obstet & Gynecol, Affiliated Hosp 2, Wenzhou 325027, Zhejiang, Peoples R China
[2] Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325027, Zhejiang, Peoples R China
[3] Wenzhou Med Univ, Affiliated Hosp 2, Dept Anaesthesiol, Wenzhou 325027, Zhejiang, Peoples R China
[4] Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325027, Zhejiang, Peoples R China
[5] Key Lab Struct Malformat Children Zhejiang Prov, Wenzhou 325000, Zhejiang, Peoples R China
来源
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY | 2023年 / 225卷
关键词
Pregnenolone; Progesterone; Inhibition; 3?-hydroxysteroid dehydrogenase 1; Phenolic compounds; Endocrine disruptors; TYPE-1; STRUCTURE/FUNCTION; PROGESTERONE; NONYLPHENOL; EXPRESSION;
D O I
10.1016/j.jsbmb.2022.106202
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human 3 beta-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 mi-crosomes 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 mu M, respectively, while 4-nonylphenol and pentabro-mophenol were noncompetitive inhibitors of rat HSD3B4 with Ki values of 20.86 and 141.8 mu M. 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.
引用
收藏
页数:11
相关论文
共 50 条
  • [1] Effects of parabens on human and rat placental 3β-hydroxysteroid dehydrogenase isoforms: Structure activity relationship and docking analysis
    Xiang, Jie
    Zhong, Mingzhu
    Zhang, Qian
    Zhu, Yang
    Pan, Peipei
    Li, Huitao
    Fei, Qianjin
    Ou, Rongying
    Ge, Ren-shan
    Zhang, Weibing
    JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2025, 245
  • [2] Inhibition of human and rat placental 3β-hydroxysteroid dehydrogenase/Δ5,4-isomerase activities by insecticides and fungicides: Mode action by docking analysis
    Li, Jingjing
    Tian, Fuhong
    Tang, Yunbing
    Shi, Lei
    Wang, Shaowei
    Hu, Zhiyan
    Zhu, Yang
    Wang, Yiyan
    Li, Huitao
    Ge, Ren-shan
    Li, Xiaoheng
    CHEMICO-BIOLOGICAL INTERACTIONS, 2023, 369
  • [3] Effects of organochlorine pesticides on human and rat 17β-hydroxysteroid dehydrogenase 1 activity: Structure-activity relationship and in silico docking analysis
    Gong, Chaochao
    Chen, Sailing
    Tang, Yunbing
    Chen, Huiqian
    Xie, Jianghuan
    Lv, Yanning
    Shen, Zhefan
    Zhu, Yang
    Wang, Shaowei
    Ge, Ren-shan
    Zhao, Junzhao
    JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2024, 240
  • [4] Effects of phthalates on 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase 3 activities in human and rat testes
    Yuan, Kaiming
    Zhao, Binghai
    Li, Xing-Wang
    Hu, Guo-Xin
    Su, Ying
    Chu, Yanhui
    Akingbemi, Benson T.
    Lian, Qing-Quan
    Ge, Ren-Shan
    CHEMICO-BIOLOGICAL INTERACTIONS, 2012, 195 (03) : 180 - 188
  • [5] EFFECTS OF PHTHALATES ON 3β-HYDROXYSTEROID DEHYDROGENASE AND 17β-HYDROXYSTEROID DEHYDROGENASE 3 ACTIVITIES IN HUMAN AND RAT TESTES
    Su, Ying
    Zhao, Binghai
    Ge, Ren-Shan
    Lian, Qing-Quan
    JOURNAL OF ANDROLOGY, 2012, 33 (02): : 70 - 71
  • [6] Effects of genistein and equol on human and rat testicular 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase 3 activities
    Hu, Guo-Xin
    Zhao, Bing-Hai
    Chu, Yan-Hui
    Zhou, Hong-Yu
    Akingbemi, Benson T.
    Zheng, Zhi-Qiang
    Ge, Ren-Shan
    ASIAN JOURNAL OF ANDROLOGY, 2010, 12 (04) : 519 - 526
  • [7] Chemicals of environmental concern as inhibitors of human placental 3?-hydroxysteroid dehydrogenase 1 and aromatase: Screening and docking analysis
    Tang, Luming
    Shi, Lei
    Tang, Yunbing
    Ying, Yingfeng
    Dong, Yaoyao
    Li, Huitao
    Ge, Ren-Shan
    CHEMICO-BIOLOGICAL INTERACTIONS, 2022, 368
  • [8] The analysis of pesticides and fungicides in the inhibition of human and rat placental 3l3-hydroxysteroid dehydrogenase activity: Mode of inhibition and mechanism
    Zhai, Yingna
    Wang, Shaowei
    Zhang, Bingru
    Tang, Yunbing
    Wang, Hong
    Li, Jingjing
    Hu, Zhiyan
    Wang, Yiyan
    Li, Huitao
    Ge, Ren-shan
    TOXICOLOGY LETTERS, 2023, 379 : 76 - 86
  • [9] GENISTEIN EXERTS INHIBITION OF HUMAN AND RAT TESTICULAR 3β-HYDROXYSTEROID DEHYDROGENASE ACTIVITY
    Zhou, Hongyu
    Hu, Guo-Xin
    Zhao, Binghai
    Chu, Yanhui
    Akingbemi, Benson
    Zheng, Zhi-Qiang
    Ge, Ren-Shan
    JOURNAL OF ANDROLOGY, 2010, : 73 - 73
  • [10] Direct inhibition of bisphenols on human and rat 1113-hydroxysteroid dehydrogenase 2: Structure-activity relationship and docking analysis
    Zhang, Bingru
    Wang, Shaowei
    Tang, Yunbing
    Hu, Zhiyan
    Shi, Lei
    Lu, Jialin
    Li, Huitao
    Wang, Yiyan
    Zhu, Yang
    Lin, Han
    Ge, Ren-shan
    ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, 2023, 254