THE ENDOGENOUS ESTROGEN METABOLITE 2-METHOXYESTRADIOL INDUCES APOPTOTIC NEURONAL CELL-DEATH IN-VITRO

We examined the effects of 2-methoxyestradiol, a metabolite of estradi ol, on cell death in retinoic acid (RA)-differentiated neuroblastoma S H-SY5Y cell cultures. Cell death was induced by 2-methoxyestradiol in a concentration-dependent manner. Estradiol and 2-methoxyestriol faile d to induce cell death. The cell death response to 2-methoxyestradiol was sensitive to the protein synthesis inhibitor cycloheximide and the apopain inhibitor Ac-Asp-Glu-Val-Asp-H (aldehyde). 2-Methoxyestradiol also induced internucleosomal DNA fragmentation. Hence we propose a r ole for an endogenous neuroactive steroid metabolite in the etiology o f some neurodegenerative diseases.