December 5, 2013
Researchers Discover Brain Actually Produces Estrogen Too
April Flowers for redOrbit.com - Your Universe Online
The brain can produce and release estrogen, according to a new study from the University of Wisconsin-Madison. This discovery could lead to a better understanding of hormonal changes observed from before birth throughout the entire aging process.
The study findings, published in the Journal of Neuroscience, reveal that the hypothalamus can directly control reproductive function in rhesus macaques. The researchers suggest that the hypothalamus could perform the same function in women.
For about 80 years, scientists have known that the hypothalamus region of the brain is involved in regulating the menstrual cycle and reproduction. The presence of natural estrogen was predicted within the past 40 years, but scientists still didn't know whether the brain could actually make and release estrogen.
The ovaries produce most estrogen, such as estradiol — a primary hormone that controls the menstrual cycle. Circulating throughout the body, including the brain and pituitary gland, estradiol influences reproduction, body weight, and learning and memory. Many normal functions are compromised when the ovaries are removed or lose functionality after menopause.
"Discovering that the hypothalamus can rapidly produce large amounts of estradiol and participate in control of gonadotropin-releasing hormone neurons surprised us," says Ei Terasawa, professor of pediatrics at the UW School of Medicine and Public Health and senior scientist at the Wisconsin National Primate Research Center. "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."
The hypothalamus may become a novel area for drug targeting for diseases that may be linked to estrogen imbalances, such as Alzheimer's disease, stroke, depression, experimental autoimmune encephalomyelitis and other autoimmune disorders. Terasawa says, "Results such as these can point us in new research directions and find new diagnostic tools and treatments for neuroendocrine diseases."
Brian Kenealy, who earned his PhD this summer in the Endocrinology and Reproductive Physiology Program at UW-Madison, said this new study "opens up entirely new avenues of research into human reproduction and development, as well as the role of estrogen action as our bodies age."
Kenealy conducted three experiments.
In the first, he administered a brief infusion of estradiol benzoate into the hypothalamus of rhesus macaques that had surgery to remove their ovaries. The infusion rapidly stimulated GnRH release.
Mild electrical stimulation of the hypothalamus was used in the second experiment, causing the release of both estrogen and GnRH (thus mimicking how estrogen could induce a neurotransmitter-like action).
In the final experiment, the team infused letrazole, an aromatase inhibitor that blocks the synthesis of estrogen, resulting in a lack of estrogen as well as GnRH release from the brain. Together, these methods demonstrated how local synthesis of estrogen in the brain is important in regulating reproductive function.
Terasawa says that the reproductive, neurological and immune systems of rhesus macaques have proven to be excellent biomedical models for humans over several decades. Terasawa's research focuses on the neural and endocrine mechanisms that control the initiation of puberty. "This work is further proof that these animals can teach us about so many basic functions we don't fully understand in humans."
Prior to this discovery, recent evidence had shown that estrogen acting as a neurotransmitter in the brain rapidly induced sexual behavior in quails and rats. Kenealy's research demonstrates the first evidence of this local hypothalamic action in primates, and in those that don't even have ovaries.
"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 says.