2-OH-estradiol, an endogenous hormone with neuroprotective functions

• Published in: Journal of psychiatric research 2003-11, Vol.37 (6), p.517-523
• Main Authors: Teepker, Michael, Anthes, Norman, Krieg, Jürgen-Christian, Vedder, Helmut
• Format: Article
• Language: English
• Subjects: 17-β-Estradiol; 2-Hydroxy-estradiol; Adult and adolescent clinical studies; Animals; Antioxidants - physiology; Behavioral psychophysiology; Biological and medical sciences; Brain - metabolism; Cell Line; Estradiol - analogs & derivatives; Estradiol - chemistry; Estradiol - metabolism; Estradiol - physiology; Female; Fundamental and applied biological sciences. Psychology; Hippocampal cells; Hippocampus - cytology; Hormones and behavior; In Vitro Techniques; Lipid Peroxidation; Male; Medical sciences; Miscellaneous; Neuroprotection; Pregnancy; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Rats; Rats, Sprague-Dawley
• ISSN: 0022-3956; 1879-1379
• DOI: 10.1016/S0022-3956(03)00068-2

We compared the neuroprotective effects of the catecholestrogen 2-hydroxy-estradiol (2-OH-E 2) to the actions of 17-β-estradiol (E 2), since catecholestrogens have been clinically implicated in the pathophysiology of major depression and other psychiatric diseases. Using the hippocampal HT22 cell line as a well-established in vitro model system, we here show that the extent of the neuroprotective effects of 2-OH-E 2 was significantly increased compared to the physiological estrogen E 2 at equimolar concentrations after a toxic challenge with hydrogen peroxide. Statistically significant effects of neuroprotection as measured by survival of HT22 cells were detectable at concentrations of 1 and 10 μM of 2-OH-E 2 or E 2. Studies on the time-dependence of the evoked reactions showed that a pre-incubation and a post-incubation up to 30 min with a dose of 10 μM of 2-OH-E 2 resulted in a significant decrease in cell death after incubation with hydrogen peroxide if compared to E 2. Further characterization of the effects in rat brain homogenates with an assay for the induction of cellular lipid peroxidation (LPO) revealed, that 2-OH-E 2 was more effective in the reduction of LPO than E 2 in equimolar concentrations. This indicates a pharmacologically relevant effect of this hormone metabolite and a mechanism of action, which does not involve the classical estrogen receptor. In conclusion, the catecholestrogen 2-OH-E 2 induces increased neuroprotective actions in comparison to the major physiological estrogen E 2, suggesting a clinically relevant physiological function of catecholestrogens during health and disease.