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

Gong, C ; Chen, S ; et al.

In: The Journal of steroid biochemistry and molecular biology, Jg. 240 (2024-06-01), S. 106510

academicJournal

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 IC 50 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 IC 50 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 IC 50 values and LogP for human 17β-HSD1, while a slight negative correlation was observed between IC 50 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.

Competing Interests: Declaration of Competing Interest No conflict interests.

Titel:	Effects of organochlorine pesticides on human and rat 17β-hydroxysteroid dehydrogenase 1 activity: Structure-activity relationship and in silico docking analysis.
Autor/in / Beteiligte Person:	Gong, C ; Chen, S ; Tang, Y ; Chen, H ; Xie, J ; Lv, Y ; Shen, Z ; Zhu, Y ; Wang, S ; Ge, RS ; Zhao, J
Zeitschrift:	The Journal of steroid biochemistry and molecular biology, Jg. 240 (2024-06-01), S. 106510
Veröffentlichung:	Oxford ; New York : Pergamon, c1990-, 2024
Medientyp:	academicJournal
ISSN:	1879-1220 (electronic)
DOI:	10.1016/j.jsbmb.2024.106510
Schlagwort:	Animals Humans Rats Structure-Activity Relationship Female 17-Hydroxysteroid Dehydrogenases antagonists & inhibitors 17-Hydroxysteroid Dehydrogenases metabolism 17-Hydroxysteroid Dehydrogenases chemistry Pregnancy Placenta metabolism Estradiol metabolism Estradiol chemistry Insecticides chemistry Insecticides pharmacology Molecular Docking Simulation Hydrocarbons, Chlorinated chemistry Hydrocarbons, Chlorinated pharmacology Pesticides chemistry Pesticides metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [J Steroid Biochem Mol Biol] 2024 Jun; Vol. 240, pp. 106510. <i>Date of Electronic Publication: </i>2024 Mar 19. MeSH Terms: Molecular Docking Simulation* ; Hydrocarbons, Chlorinated* / chemistry ; Hydrocarbons, Chlorinated* / pharmacology ; Pesticides* / chemistry ; Pesticides* / metabolism ; Animals ; Humans ; Rats ; Structure-Activity Relationship ; Female ; 17-Hydroxysteroid Dehydrogenases / antagonists & inhibitors ; 17-Hydroxysteroid Dehydrogenases / metabolism ; 17-Hydroxysteroid Dehydrogenases / chemistry ; Pregnancy ; Placenta / metabolism ; Estradiol / metabolism ; Estradiol / chemistry ; Insecticides / chemistry ; Insecticides / pharmacology Contributed Indexing: Keywords: 17β-HSD1; BeWo cells; Docking analysis; Estradiol; Organochlorine pesticides Substance Nomenclature: 0 (Hydrocarbons, Chlorinated) ; 0 (Pesticides) ; EC 1.1.- (17-Hydroxysteroid Dehydrogenases) ; 4TI98Z838E (Estradiol) ; 0 (Insecticides) Entry Date(s): Date Created: 20240320 Date Completed: 20240430 Latest Revision: 20240501 Update Code: 20240502

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