A new study published this month in the Journal of Neuroscience has shed some light on to the mysterious ways that hormones work in the brain.
Estrogen is a hormone produced by the ovaries in women, and it plays a major role in the reproductive cycle. Men make estrogen, too, but in much smaller quantities. In men, a special enzyme converts testosterone into estrogen. In both men and women, estrogen also plays a role in regulating body weight.
Estrogen is active in the brain as well, and is involved in regulating learning, memory, and mood. Recent studies have shown that when the brain is at risk, such as during a stroke or traumatic injury, estrogen helps to protect the brain from damage. But until now, scientists thought that all of the brain’s estrogen came from other parts of the body.
Hormones on the Brain
The study, led by Ei Terasawa, a professor at the Wisconsin National Primate Research Center at the University of Wisconsin-Madison, examined the brains of rhesus monkeys, which have a very similar reproductive system to humans. Terasawa's team found that the hypothalamus, a region of the brain that controls how the ovaries produce estrogen, is also able to produce new estrogen on its own.
"Discovering that the hypothalamus can rapidly produce large amounts of [estrogen] surprised us," said Terasawa in a press release. "These findings not only shift the concept of how reproductive function and behavior is regulated, but have real implications for understanding and treating a number of diseases and disorders."
Estrogen imbalances are thought to play a role in several brain disorders, including Alzheimer’s disease, stroke, and autoimmune disorders. New drugs to target the hypothalamus might someday be the key to treatment.
The Brain Giveth...and Taketh Away
The study covers three experiments performed by first author Brian Kenealy. In the first experiment, Kenealy removed the ovaries of rhesus monkeys, which prevented them from generating estrogen there. He then administered a dose of estrogen to the monkeys' hypothalamus, triggering the hormonal pathway that normally tells the ovaries to produce large amounts of estrogen. Without the ovaries in play, the brain took over, creating new estrogen that washed over the brain in large, rapid pulses.
In the second experiment, Kenealy stimulated the hypothalamus directly using a mild electric current, causing it to release estrogen. Not only did this confirm that the hypothalamus can make its own estrogen, but it also suggests that estrogen can act not just as a hormone, but also as a neurotransmitter in the brain. Neurotransmitters are the chemicals that nerve cells use to communicate with one other inside the brain, triggering the electrical currents that make up brain activity.
Finally, in the third experiment, Kenealy injected a drug called letrozole into the hypothalamus, which blocks the enzymes that create estrogen. With this drug in play, the brain stopped releasing estrogen.
Together, these experiments demonstrate that the brain has its own methods of estrogen production that are independent from the female reproductive cycle.
"The discovery that the primate brain can make estrogen is key to a better understanding of hormonal changes observed during every phase of development, from prenatal to puberty, and throughout adulthood, including aging," Kenealy said.