Abstract
The notion that epigenetics may play an important role in the establishment and maintenance of sex differences in the brain has garnered great enthusiasm but the reality in terms of actual advances has been slow. Two general approaches include the comparison of a particular epigenetic mark in males vs. females and the inhibition of key epigenetic enzymes or co-factors to determine if this eliminates a particular sex difference in brain or behavior. The majority of emphasis has been on candidate genes such as steroid receptors. Only recently have more generalized survey type approaches been achieved and these promise to open new vistas and accelerate discovery of important roles for DNA methylation, histone modification, genomic imprinting and microRNAs (miRs). Technical challenges abound and, while not unique to this field, will require novel thinking and new approaches by behavioral neuroendocrinologists.
Highlights
At the frontier of epigenetics of brain sex differencesThe notion that epigenetics may play an important role in the establishment and maintenance of sex differences in the brain has garnered great enthusiasm but the reality in terms of actual advances has been slow
In 2009 a minisymposium was held at the annual meeting of the Society for Neuroscience titled ‘‘Epigenetics of Sex Differences in the Brain’’
Matsuda et al (2011) took a slightly different approach and explored the epigenetic regulation of genes already known to be central to the process of masculinization of sexual behavior: estrogen receptor (Esr1), or estrogen receptor alpha (ERα) and Cyp19a or aromatase, the enzyme that converts testosterone to estradiol
Summary
The notion that epigenetics may play an important role in the establishment and maintenance of sex differences in the brain has garnered great enthusiasm but the reality in terms of actual advances has been slow. Epigenetics is increasingly a general term that encompasses many and varied specifics These include changes to the DNA via methylation, which become more and more complicated the more we learn, changes to the histones of which there is not quite an infinite variety but something close, imprinting, a still mysterious process of allelic regulation especially in the brain, and microRNAs (miRs) which can impact multiple genes simultaneously. Effective masculinization of female pups with exogenous estradiol injection requires an enormous dose, ten times that used in a full grown adult to induce sexual receptivity This rather bizarre scenario raises some interesting questions; how does such a small and transient sex difference in steroid levels have such a profound effect?
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