Differences between male and female brains develop through a complex train of events involving actions of the hormone estrogen in the fetal brain. A protein called alpha-fetoprotein (AFP) binds to and regulates gender-determining estrogen during fetal development, but its exact function has remained unclear. Now, Julie Bakker and colleagues answer this longstanding question in the February 2006 issue of Nature Neuroscience.
In male fetuses, testosterone produced in the testes is converted to estrogen, which powerfully influences protein expression in the developing male brain. Female fetuses produce no testosterone and have much lower levels of brain estrogen, mostly derived from the mother's ovaries. It was unknown whether AFP works to transport the little available estrogen into the brain for efficient use or to prevent estrogen's 'masculinizing' influence by binding to it and keeping it out of the brain. The authors found that female mice without the AFP gene behaved more like males as adults, and that certain structures in their brains were masculinized. When the authors blocked estrogen production in pregnant mice bearing fetuses without AFP -- so that female fetuses had no circulating estrogen at all -- mice grew up to behave like normal females.
These results suggest that, in normal female fetuses, AFP acts to keep estrogen out of the developing brain. Paradoxically, this hormone, which is normally associated with females, promotes masculine brain development during the prenatal period, and AFP protects female brains from its influence. The new findings help to explain why female fetuses are not masculinized by hormones coming from their male neighbors in the womb..
Julie Bakker (University of Liege, Belgium)
Additional contact for comment on paper:
S. Marc Breedlove (Michigan State University, East Lansing, MI, USA)
Abstract available online.
(C) Nature Neuroscience press release.
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