Mounting evidence indicates that members of the estrogen family of sex hormones can morph into neurotransmitters in the brain, fulfilling an unexpected role. The latest study comes from a team at Johns Hopkins University and the University of Liège in Belgium. Researchers manipulated the amounts of estradiol (a form of estrogen) in the brains of quail by injecting a compound that suppresses estradiol production. Within minutes the birds exhibited dramatic changes in sexual activity and pain thresholds. Hormones cannot achieve signaling speeds that fast, says Gregory Ball, a professor of psychological and brain sciences at Johns Hopkins who led the work. Humans have similar molecular mechanisms in their brains.

Estrogens interact with various groups of cells in the body, such as breast and uterus tissue, and with neurons in the brain. When estrogens act as hormones, they travel through the membrane of a cell to the nucleus, where they switch genes on or off, thereby regulating protein production. The timescale for the resulting effects, such as the stimulation of menstrual cycles, lies on the order of days, months or even years. The neurotransmitter estrogen docks directly to the outer membrane of neurons, initiating direct communication among the cells. The quick firing triggers actions within minutes or seconds.

The discovery of the estrogen signaling system could adjust the prevailing model of how neurons communicate, as well as clinical interventions for certain brain conditions that involve estrogens, Ball says. He notes that estrogens act quickly on pain thresholds and therefore “might be very useful when thinking about pain-control medication.”