Estrogen: Not just produced by the ovaries

by Jordana Lenon

A University of Wisconsin-Madison research team reports today that the brain can produce and release estrogen—a discovery that may lead to a better understanding of hormonal changes observed from before birth throughout the entire aging process.

The new research shows that the hypothalamus can directly control reproductive function in rhesus monkeys and very likely performs the same action in women.

Scientists have known for about 80 years that the hypothalamus, a region in the , is involved in regulating the and reproduction. Within the past 40 years, they predicted the presence of neural estrogens, but they did not know whether the brain could actually make and release estrogen.

Most estrogens, such as estradiol, a primary hormone that controls the menstrual cycle, are produced in the ovaries. Estradiol circulates throughout the body, including the brain and pituitary gland, and influences reproduction, body weight, and learning and memory. As a result, many normal functions are compromised when the ovaries are removed or lose their function 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."

For diseases that may be linked to estrogen imbalances, such as Alzheimer's disease, stroke, depression, experimental autoimmune encephalomyelitis and other autoimmune disorders, the hypothalamus may become a novel area for drug targeting, Terasawa says. "Results such as these can point us in new research directions and find new diagnostic tools and treatments for neuroendocrine diseases."

The study, published today in the Journal of Neuroscience, "opens up entirely new avenues of research into human reproduction and development, as well as the role of estrogen action as our bodies age," reports the first author of the paper, Brian Kenealy, who earned his Ph.D. this summer in the Endocrinology and Reproductive Physiology Program at UW-Madison. Kenealy performed three studies. In the first experiment, a brief infusion of estradiol benzoate administered into the hypothalamus of that had surgery to remove their ovaries rapidly stimulated GnRH release. The brain took over and began rapidly releasing this estrogen in large pulsing surges.

In the second experiment, mild electrical stimulation of the caused the release of both estrogen and GnRH (thus mimicking how estrogen could induce a neurotransmitter-like action). Third, the research 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.

The reproductive, neurological and immune systems of rhesus macaques have proven to be excellent biomedical models for humans over several decades, says Terasawa, who 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."

Leading up to this discovery, Terasawa said, recent evidence had shown that estrogen acting as a neurotransmitter in the brain rapidly induced sexual behavior in quails and rats. Kenealy's work is 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 is key to a better understanding of observed during every phase of development, from prenatal to puberty, and throughout adulthood, including aging," Kenealy says.

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JVK
not rated yet Dec 04, 2013
http://www.hawaii...ion.html

From our 1996 Hormones and Behavior review article:

Excerpt: "Relatively new, however, is the realization that various portions of the CNS itself can produce steroids and can do so independently of the gonads and adrenals (Baulieu and Robel, 1990; Roselli, 1995). These "neurosteroids" (steroids produced by neurons) have been reported in the fetal brain, suggesting localized organizational effects (Kabbadj, el-Etr, Baulieu, and Robel, 1993). Activational effects in sexual behavior have also been shown for neurosteroids (Genazzani, Palumbo, de Micheroux, Artini, Criscuolo, Ficarra, Guo, Benelli, Bertolini, Petraglia, and Purdy, 1995), even at intermediate levels of a steroid conversion sequence (Kavaliers and Kinsella, 1995).

Though neurosteroids research is relatively new, certain findings already are important....
rbogle
not rated yet Dec 06, 2013
Estrogens are produced by other tissues such as the liver, adrenal glands, and the breasts. Additionally, many tissues synthesize estrogens from androgen. According to the paper Estrogen production and action, Nelson LR, Bulun SE. J Am Acad Dermatol. 2001, the enzyme aromatase is found in a number of human tissues and cells, including the brain, and it locally catalyzes the conversion of steroids to estrogens.

Apparently, estrogen is being produced all the time in many diverse areas of the body. The "discovery" announced here is much ado about nothing. It's telling that the details of what was actually done to the monkeys used by Kenealy (and Terasawa) and what the impacts to them were weren't described in any detail.