ArticleBMC pharmacology & toxicology2022
The inhibition of tamoxifen on UGT2B gene expression and enzyme activity in rat liver contribute to the estrogen homeostasis dysregulation.
Article in BMC pharmacology & toxicology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 14 citations in OpenAlex.
- Pharmacotherapeutic considerations of selective estrogen receptor modulators for vascular protection.Frontiers in pharmacology · 2026Review
- The role of estrogen in Alzheimer's disease pathogenesis and therapeutic potential in women.Molecular and cellular biochemistry · 2025Review
- Cardamom extract alleviates tamoxifen-induced liver damage by suppressing inflammation and pyroptosis pathway.Scientific reports · 2025Article
- Jujuboside A Attenuates Polycystic Ovary Syndrome Based on Estrogen Metabolism Through Activating AhR-mediated CYP1A2 Expression.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
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10 authors at 2 institutions in 1 country.
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Abstract
backgroundTamoxifen treatment may induce dysregulation of estrogen homeostasis, leading to the occurrence of related adverse reactions. However, the potential mechanisms are still unclear. The purpose of the present study was to uncover whether tamoxifen treatment would act on estrogen metabolism-related biological enzymes and the regulatory effect on estrogen homeostasis to clarify the key factors and potential mechanisms of adverse reactions caused by long-term use of tamoxifen.
methodFemale SD rats were administrated with tamoxifen CMC-Na solution (p.o.) once daily for four weeks and then housed at room temperature. Serum, breast, liver, uterus, and ovarian tissues were obtained, and the effects of tamoxifen administration on estrogen homeostasis, the expression, and activity of estrogen metabolic enzyme were evaluated.
resultsCompared with the control group, the estrogen homeostasis was disturbed and the expression and activity of UGT2B1 (homology with human UGT2B7) were significantly reduced in the rats administrated with tamoxifen. The inhibitory effect of tamoxifen on UGT2B7 was dominated by hydrophobic and π-π stacking interactions, resulting in a concentration-dependent inhibition of UGT2B7 activity by tamoxifen and the imbalance of ligand-activated transcription factors, leading to abnormal regulation of UGT2B and disturbance of estrogen homeostasis, which in turn led to adverse reactions of tamoxifen.
conclusionWe established links between estrogen metabolism and tamoxifen administration and we proposed that the UGT2B inhibition was involved in the disturbance of estrogen homeostasis and the occurrence of tamoxifen-related adverse reactions.
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