The impact of ovariectomy and chronic estrogen treatment on gene expression in the rat cortex: Implications for psychiatric disorders

Estrogens, via estrogen-mediated changes in CNS function, have been suggested to be beneficial in the treatment of several psychiatric disorders. Few studies have used transcriptomic technologies to determine the effect of estrogen on gene expression in the CNS. Thus, we aimed to examine the impact of ovariectomy (the removal of all ovarian hormones) and estrogen replacement on rat frontal cortical gene expression. We used the Agilent SurePrint G3 Gene Expression Rat Array to measure levels of RNA in intact (cycling) female rats and in ovariectomized rats that were, or were not, given 17?-estradiol in implants for 4 weeks. Compared to untreated ovariectomized rats, intact rats (effect of ovarian hormones; comparison 1) and rats receiving 17?-estradiol replacement (estrogen-specific effects; comparison 2) showed significant changes in cortical gene expression (58 and 36 genes, respectively). These changes in gene expression would be expected to affect pathways that regulate neurotransmitters, glutathione and sphingolipids; pathways known to be implicated in the pathophysiologies of psychiatric disorders. When we compared the levels of gene expression in the two comparisons that had a significance of p < 0.01 independent of magnitude of change, there was a strong correlation between fold changes in gene expression for 127 genes. We posit that this correlation is due to the level of expression of these genes being strongly influenced by both cycling and replacement estrogen. Further exploration of ovarian hormoneand estrogen-sensitive gene expression may provide new insight into the aetiology of aspects of psychiatric disorders that show sex differences.