黑料吃瓜资源

Sex hormones play an important role in shaping an animal鈥檚 behavior, and their influence starts early. Early-life hormonal surges help shape the developing brain, establishing circuitry that will influence behavior for a lifetime.

Hundreds of genes in the brain fall under the control of estrogen. Fluctuating levels of the hormone cause shifts in mood, energy balance, and behavior throughout life, in addition to sculpting developing neural circuits early on. These effects occur when activated estrogen receptors sit directly on a cell鈥檚 DNA to turn genes on or off.

黑料吃瓜资源 Assistant Professor Jessica Tollkuhn, graduate student Bruno Gegenhuber, and their colleagues, have been mapping exactly where estrogen receptors latch onto DNA inside mouse brain cells. They鈥檝e looked at both males and females and compared the brains of adults to the still-developing brains of young pups. In the journal Nature, they report on the hormone receptor鈥檚 targets in the brain and show that estrogen sets up physical differences in the brains of males and females during development.

Tollkuhn explains that estrogen is present in the brains of both males and females: some neurons make it themselves out of testosterone. In male mice, estrogen generated through a surge of testosterone that is released soon after birth shapes developing circuitry. As a result, certain brain regions are larger and contain more cells in males than they do in females鈥攁 difference that affects a range of behaviors in adulthood, including mating, parenting, and aggression.

鈥淭here’s this critical period when the brain is developing and wiring up that it has to get this input in order to make these permanent changes in the brain wiring. This is a transient surge, but it seems to have extremely long-lasting effects on brain development.鈥�

Tollkuhn鈥檚 team examined where estrogen receptors landed after this hormonal surge, focusing on a brain region called the BNST, which is larger in males than females in both mice and humans. They found a host of genes that were under estrogen鈥檚 control, including many involved in neurodevelopment and neuronal signaling. And although estrogen itself remains in the brain for only a few hours, it seems that the hormone-controlled genes remain active for weeks.

Now that they know what genes estrogen is targeting in the brain, Tollkuhn鈥檚 team plans to explore exactly how those genes mediate the hormone鈥檚 diverse effects on brain development, behavior, and disease.

Written by: Jennifer Michalowski, Science Writer | [email protected] | 516-367-8455

Funding

Stanley Family Foundation, National Institutes of Health, Simons Foundation

Citation

Gegenhuber, B., et al., 鈥淕ene regulation by gonadal hormone receptors underlies brain sex differences鈥�, Nature, May 5, 2022. DOI: