In mammals, gonadal steroid hormones regulate sex differences in neural activity and behavior
by establishing circuits during critical periods of development and triggering the display of
innate social skills in adulthood. Among these, estradiol is the main regulator of differentiation
in mice.

Hundreds of genes in the brain are under the control of estrogen. Fluctuating levels of the
hormone cause changes in mood, energy balance, and behavior throughout life, as well as
sculpt developing neural circuits early on. These effects occur when receptors sit directly on a
cell’s DNA to turn genes on or off. Estrogen coordinates gender mismatches in neural circuitry.

In conclusion, the estrogen receptor transcription factor orchestrates brain sexual
differentiation through two mechanisms: establishing two types of male-biased neurons and
activating a gene expression program that sustains it.

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