4-Hydroxyestrone

4-Hydroxyestrone (4-OHE1) is a brain-penetrant estrogen metabolite. 4-Hydroxyestrone shows neuroprotective effects involving increased cytoplasmic localization of p53 resulting from SIRT1-mediated p53 deacetylation. 4-Hydroxyestrone relies on PDI to mediate its protective effect against chemically induced ferroptosis in estrogen receptor-negative cancer cells. 4-Hydroxyestrone inhibits lipid peroxidation and lipid-ROS accumulation. 4-Hydroxyestrone blocks preovulatory luteinizing hormone surges in Rattus norvegicus. 4-Hydroxyestrone can be used for the researches of neurodegeneration, breast cancer and endocrine disease^[1][2][3]. In Vitro:4-Hydroxyestrone (2.5-10 μM; 24 h) strongly protects HT22 immortalized mouse hippocampal neuronal cells against glutamate-induced oxidative cell death^[1].
4-Hydroxyestrone (5 μM; 4-24 h) induces cytoplasmic translocation of p-p53^(Ser15) in HT22 immortalized mouse hippocampal neuronal cells treated with 5 mM glutamate, reversing glutamate-induced nuclear accumulation of p-p53^(Ser15) over 4-24 hours^[1].
4-Hydroxyestrone (5 μM; 4-24 h) promotes cytoplasmic accumulation of p-MDM2^(Ser166) in HT22 immortalized mouse hippocampal neuronal cells treated with 5 mM glutamate, reversing glutamate-induced nuclear accumulation of p-MDM2^(Ser166) over 4-24 hours^[1].
4-Hydroxyestrone (5 μM; 24 h) inhibits glutamate-induced p53 transcriptional activity in HT22 immortalized mouse hippocampal neuronal cells by reducing GADD45α mRNA and protein levels, correlating with improved cell viability after 24-hour co-incubation^[1].
4-Hydroxyestrone (5 μM) maintains SIRT1 protein levels and function in HT22 immortalized mouse hippocampal neuronal cells treated with 5 mM glutamate, mediating p53 deacetylation and cytoplasmic translocation to exert neuroprotection^[1].
4-Hydroxyestrone (0.5-8 μM; 12-24 h) strongly protects estrogen receptor-negative MDA-MB-231 human breast cancer cells from Erastin (HY-15763)-induced ferroptotic cell death in a concentration-dependent manner^[2].
4-Hydroxyestrone (1-8 μM; 24 h) strongly protects estrogen receptor-negative HCC1937 human breast cancer cells from Erastin + BSO (HY-106376)-induced ferroptotic cell death in a concentration-dependent manner^[2].
4-Hydroxyestrone (4-8 μM; 12 h) abrogates Erastin-induced lipid peroxidation and lipid-ROS accumulation in estrogen receptor-negative MDA-MB-231 and HCC1937 human breast cancer cells^[2].
4-Hydroxyestrone (0.0625-64 μM; 3 h) binds to PDI in live MDA-MB-231 human breast cancer cells, stabilizing the protein against thermal denaturation in a concentration-dependent manner^[2].
4-Hydroxyestrone (10 μM) directly inhibits the catalytic activity of wild-type human PDI, but not PDI^H256A mutant^[2].
4-Hydroxyestrone (8 μM; 12 h) inhibits Erastin-induced iNOS dimerization and subsequent NO accumulation in estrogen receptor-negative MDA-MB-231 human breast cancer cells^[2].
4-Hydroxyestrone (4-8 μM; 24 h) relies on PDI to mediate its protective effect against chemically induced ferroptosis in estrogen receptor-negative MDA-MB-231 and HCC1937 human breast cancer cells^[2]. In Vivo:4-Hydroxyestrone (10 µg/rat; s.c.; daily; 7 days) provides near-complete neuroprotection against Kainic acid (HY-N2309)-induced hippocampal oxidative damage and working memory impairment in male Sprague-Dawley rats^[1].
4-Hydroxyestrone (100 μg; i.v.; single injection) effectively inhibits the preovulatory LH surge in 86% of 4-day cycling rats when administered at 0900 h on proestrus, but is completely ineffective when given at 1000 h or 1200 h^[3].