Methoxychlor and its metabolite HPTE inhibit rat neurosteroidogenic 3α-hydroxysteroid dehydrogenase and retinol dehydrogenase 2
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Updated: Feb 6, 2026

Mapping Metabolism: Monitoring Lactate Dehydrogenase Activity Directly in Tissue
Published on: June 21, 2018
Baiping Mao1, Chengyun Wu2, Wenwen Zheng1
1Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Abstract:
Methoxychlor is primarily used as an insecticide and it is widely present in the environment. The objective of the present study was to investigate the direct effects of methoxychlor and its metabolite hydroxychlor (HPTE) on rat neurosteroidogenic 3α-hydroxysteroid dehydrogenase (AKR1C14) and retinol dehydrogenase 2 (RDH2) activities. Rat AKR1C14 and RDH2 were cloned and expressed in COS-1 cells, and the effects of methoxychlor and HPTE on these enzymes were measured. HPTE was more potent to inhibit AKR1C14 and RDH2 activities than methoxychlor, with IC50 values of 2.602 ± 0.057 μM and 20.473 ± 0.049 μM, respectively, while those of methoxychlor were over 100 μM. HPTE competitively inhibited AKR1C14 and RDH2 when steroid substrates were used, while it showed a mode of mixed inhibition on these enzymes when NADPH/NAD+ were used. We elucidated the binding mode of methoxychlor and HPTE to the crystal structure of AKR1C14 by molecular docking and found that HPTE had higher affinity with the enzyme than methoxychlor. In conclusion, HPTE is more potent than methoxychlor to inhibit both AKR1C14 and RDH2.
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