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 behavioral neuroscientist said.
Gregory Ball, professor in the Krieger School's
Psychological and Brain Sciences, has added to that
evidence with an article, written with a Belgian
collaborator, to be published in the May issue of Trends
Their research, studying a form of estrogen called
estradiol 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," he said.
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
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
"Quail, especially, are useful for the study of
estrogen synthesis because they express a high level of
aromatase activity in the brain," Ball said, referring to
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.