Steroid hormones have wide-ranging organizational, activational and protective actions in the brain. In particular, the organizational effects of early exposure to 17β-estradiol (E2) and glucocorticoids are essential for long-lasting behavioral and cognitive functions. Both steroid hormones mediate many of their actions through intracellular receptors that act as transcription factors. In the rodent cerebral cortex, estrogen receptor mRNA and protein expression are high early in postnatal life and declines dramatically as the animal approaches puberty. An understanding of the molecular mechanisms driving this developmental regulation of gene expression is critical for understanding the complex events that determine lasting brain physiology and prime the plasticity of neurons. Gene expression can be suppressed by the epigenetic modification of the promoter regions by DNA methylation that results in gene silencing. Indeed, the decrease in ERα mRNA expression in the cortex during development is accompanied by an increase in promoter methylation. Numerous environmental stimuli can alter the DNA methylation that occurs for ERα, glucocorticoid receptors, as well as many other critical genes involved in neuronal development. For example, maternal behavior toward pups can alter epigenetic regulation of ERα mRNA expression. Additionally perinatal stress and exposure to environmental estrogens can also have lasting effects on gene expression by modifying DNA methylation of these important genes. Taken together, there appears to be a critical window during development where, outside factors that alter epigenetic programming can have lasting effects on neuronal gene expression.
|Number of pages||4|
|Journal||International Journal of Developmental Neuroscience|
|State||Published - Oct 2013|
Bibliographical noteFunding Information:
This work cited from our laboratory was supported by the National Science Foundation ( NSF IOS0919944 and NSF IOS1121129 ) (MEW) and COBRE grant P20 RR15592 from the National Center for Research Resources (NCRR) . All opinions, findings and conclusions expressed in this material are those of the authors and not those necessarily of NSF or NCRR.
- DNA methylation
- Estrogen receptor
- Glucocorticoid receptor
ASJC Scopus subject areas
- Developmental Neuroscience
- Developmental Biology