Alteration in estrogen receptor alpha 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 alpha (ERalpha) mRNA levels may exist in MMI patients.


METHODS
We used Northern blot analysis to survey the expression of ERalpha mRNA transcripts in brain and body, detected by our human ERalpha riboprobe and in situ hybridization, to examine the expression pattern and quantify ERalpha 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 ERalpha mRNA transcript. By in situ hybridization, ERalpha mRNA was detected in all layers of DLPFC and all hippocampal subfields in all subjects. We detected greater DLPFC ERalpha mRNA expression in male compared with female MDD subjects and reduced ERalpha mRNA levels in the dentate gyrus of schizophrenics compared with control subjects.


CONCLUSIONS
Our results suggest that alterations in ERalpha mRNA levels exist in distinct telencephalic regions in male and female MDD patients, and in both genders in schizophrenia.
Perlman
William R
WR
Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, U.S. Department of Health and Human Services, MD 20892-1385, USA.
Tomaskovic-Crook
Eva
E
Montague
Deidra M
DM
Webster
Maree J
MJ
Rubinow
David R
DR
Kleinman
Joel E
JE
Weickert
Cynthia Shannon
CS
D000328:Adult; D000679:Amygdala / Q000737:chemistry / Q000378:metabolism; D001714:Bipolar Disorder / Q000175:diagnosis / Q000378:metabolism; D015152:Blotting, Northern; D018891:Dentate Gyrus / Q000737:chemistry / Q000378:metabolism; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000032:analysis / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry / Q000378:metabolism*; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis / Q000378:metabolism*; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000737:chemistry / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D012559:Schizophrenia / Q000175:diagnosis / Q000378:metabolism; D012737:Sex Factors
D047628:Estrogen Receptor alpha; D012313:RNA