Alteration in Estrogen Receptor α mRNA Levels in Frontal Cortex and Hippocampus of Patients with Major Mental Illness

Background Gender differences have been described in major mental illnesses (MMI). The dorsolateral prefrontal cortex (DLPFC) and hippocampus are estrogen-sensitive brain regions structurally and functionally altered in patients with MMI. We hypothesized that gender-specific alterations in DLPFC and hippocampus estrogen receptor α (ERα) mRNA levels may exist in MMI patients. Methods We used Northern blot analysis to survey the expression of ERα mRNA transcripts in brain and body, detected by our human ERα riboprobe and in situ hybridization, to examine the expression pattern and quantify ERα mRNA levels in DLPFC and anterior hippocampus of patients with major depressive disorder (MDD), schizophrenia, and bipolar disorder compared with normal control subjects. Results Northern blotting revealed brain-region-specific differences in expression levels of a 5 kb ERα mRNA transcript. By in situ hybridization, ERα mRNA was detected in all layers of DLPFC and all hippocampal subfields in all subjects. We detected greater DLPFC ERα mRNA expression in male compared with female MDD subjects and reduced ERα mRNA levels in the dentate gyrus of schizophrenics compared with control subjects. Conclusions Our results suggest that alterations in ERα mRNA levels exist in distinct telencephalic regions in male and female MDD patients, and in both genders in schizophrenia.