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Sex-Related Hormone Also A Brain Signaling Chemical


April 17, 2006, Evidence is mounting that estrogen, a hormone critical to a woman’s sexual development, should also be thought of as a neurotransmitter when acting in the brain, a Johns Hopkins University behavioral neuroscientist said.

Gregory Ball, professor in the Department of Psychological and Brain Sciences in the university’s Krieger School of Arts and Sciences, has added to that evidence with an article, written with a Belgian collaborator, to be published in the May issue of Trends in Neuroscience.

Their research, studying estradiol (a form of estrogen) in the brains of quail, suggested that estrogen in its role as a neurotransmitter, or brain signaling chemical, helps to regulate male sexual activity and the levels at which pain is perceived.

“How we categorize estradiol is of more than semantic interest,” Ball said of adding the “neurotransmitter” label to the estrogen’s traditional label of “hormone.” “It influences how scientists conduct research, the kind of experiments we do, and even the way we design clinical interventions that involve actions of estrogen in the brain.”

The journal article was written by Ball and collaborator Jacques Balthazart of the Center for Cellular and Molecular Neurobiology at the University of Liege.

In the article, the team argues that brain estrogens display many, if not all, of the functional characteristics of neurotransmitters. They are released at synapses (the tiny spaces between neurons) and act rapidly (often within minutes) to affect the activity of neighboring cells.

In contrast, hormones have traditionally been defined as compounds that are released from endocrine glands and act slowly (over hours and days) upon distant sites within the body.

Estrogen’s effect in developing a girl’s body when she reaches puberty is a classic example of a hormone’s activity. But studies on quail in both Ball’s and Balthazart’s laboratories reveal that estradiol made in the brain impacts neighboring neurons over a relatively rapid timeframe.

“Quail, especially, are useful for the study of estrogen synthesis because they express a high level of aromatase activity in the brain,” Ball said.
(Aromatase is an enzyme that promotes the conversion of androgens -- including testosterone -- into estrogens.) “This work shows that estradiol has a relatively rapid action on an adjacent cell, but the time course of this action can be fine-tuned by a rapid decrease in the activity of the enzyme that synthesizes the estrogen, thus leading to changes in the amount of estrogen available for action.”

Previous work on brain estradiol regulation had identified mechanisms involving changes in the expression of the gene for aromatase that occurred over hours, days and even weeks. Ball and Balthazart’s work has established a more rapid mechanism that involves a change in the fine chemical structure of the enzyme via a process called phosphorylation. This rapid regulation and action of brain estrogens is significant for more than just cellular action. It also can regulate aspects of male sexual behavior and pain thresholds, the researchers say.

“In the past, scientists have always assumed that the action of estrogens on brain function required at least a few hours or days to produce detectable results,” Ball said. “For this reason, relatively little attention was paid to responses that might occur more rapidly. The recent demonstration that estrogen production and action can change dramatically within minutes will change our thinking about when we should consider estrogen to be important in regulating behavior and physiology.”

Funding for Ball’s research was provided by the National Institute of Mental Health. A pdf copy of the Trends in Neuroscience article is available. Contact Lisa De Nike at or 443-287-9960.


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