A area of the mouse mind, referred to as the mattress nucleus of the stria terminalis, is bigger in males than females. Many neurons (inexperienced) produce the estrogen receptor. A selected inhabitants of those neurons (labeled for a protein referred to as Nfix in purple) is extra plentiful in males than in females. CSHL Assistant Professor Jessica Tollkuhn and her staff recognized genes focused by estrogen in neurons that coordinate intercourse variations in neural circuits. Credit: Bruno Gegenhuber/Tollkuhn lab/CSHL, 2022
Sex hormones play a big function in shaping an animal’s conduct, and their impact begins early. Early-life hormonal surges assist form the growing mind, establishing circuitry that can affect conduct for a lifetime.
Hundreds of genes within the mind fall underneath the management of estrogen. Fluctuating ranges of the hormone trigger shifts in temper, power stability, and conduct all through life, along with sculpting growing neural circuits early on. These results happen when activated estrogen receptors sit instantly on a cell’s DNA to turn genes on or off.
Cold Spring Harbor Laboratory 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’ve looked at both males and females and compared the brains of adults to the still-developing brains of young pups. In a study published today (May 4, 2022) in the journal Nature, they report on the hormone receptor’s 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—a difference that affects a range of behaviors in adulthood, including mating, parenting, and aggression.
“There’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.”
Tollkuhn’s 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’s 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’s team plans to explore exactly how those genes mediate the hormone’s diverse effects on brain development, behavior, and disease.
Reference: “Epigenetic regulation of brain sexual differentiation by estrogen receptor alpha” by B. Gegenhuber, M. V. Wu, R. Bronstein and J. Tollkuhn, 4 May 2022, Nature.
DOI: 10.1038/s41586-022-04686-1
