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Effects of organochlorine pesticides on human and rat 17ß-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.
Afiliación
  • Gong C; Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou, Zhej
  • Chen S; Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
  • Tang Y; Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
  • Chen H; Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
  • Xie J; Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
  • Lv Y; Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
  • Shen Z; Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
  • Zhu Y; Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou, Zhej
  • Wang S; Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
  • Ge RS; Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou, Zhej
  • Zhao J; Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. Electronic address: z.joyce08@163.com.
J Steroid Biochem Mol Biol ; 240: 106510, 2024 06.
Article en En | MEDLINE | ID: mdl-38508472
ABSTRACT
The objective of this study was to examine the effect of 11 organochlorine pesticides on human and rat 17ß-Hydroxysteroid dehydrogenase 1 (17ß-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 17ß-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 17ß-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 17ß-HSD1. Bivariate correlation analysis showed a positive correlation between IC50 values and LogP for human 17ß-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 17ß-HSD1, as well as their impact on hormone production.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plaguicidas / Simulación del Acoplamiento Molecular / Hidrocarburos Clorados Límite: Animals / Female / Humans / Pregnancy Idioma: En Revista: J Steroid Biochem Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plaguicidas / Simulación del Acoplamiento Molecular / Hidrocarburos Clorados Límite: Animals / Female / Humans / Pregnancy Idioma: En Revista: J Steroid Biochem Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido