The Brain Can Produce And Release Estrogen

Ovaries are not the only source of estrogen, a new study reports.

The discovery may lead to a clearer understanding of hormonal changes from before birth through the aging process.

New research from University of Wisconsin-Madison shows that the hypothalamus can directly control reproductive function in rhesus monkeys and very likely performs the same action in women.

It has been known by scientists for about 80 years that the hypothalamus, a region in the brain, is involved in regulating the menstrual cycle and reproduction.

In 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.

Concept Shifting Discovery

“Discovering that the hypothalamus can rapidly produce large amounts of estradiol and participate in control of gonadotropin-releasing hormone neurons surprised us,” said Ei Terasawa, UW School of Medicine and Public Health professor. “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 majority of estrogens, such as estradiol, a hormone controlling the menstrual cycle, are produced in the ovaries.

Estradiol circulates all through the body, including the brain and pituitary gland. It 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.

Estrogen Imbalance Drug Targeting

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

First author of the paper Brian Kenealy, says the 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.”

Three Experiments

Kenealy performed three studies. In the first, a short infusion of estradiol benzoate was administered into the hypothalamus of rhesus monkeys that had surgery to remove their ovaries rapidly stimulated GnRH release. The brain took over and began rapidly releasing this estrogen in large surges.

The second experiment involved mild electrical stimulation of the hypothalamus. This caused the release of both estrogen and GnRH, thereby mimicking how estrogen could induce a neurotransmitter-like action.

In the third experiment, 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.
Jointly, 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 been established as 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.”

“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.

Reference:

B. P. Kenealy, A. Kapoor, K. A. Guerriero, K. L. Keen, J. P. Garcia, J. R. Kurian, T. E. Ziegler, E. Terasawa.
Neuroestradiol in the Hypothalamus Contributes to the Regulation of Gonadotropin Releasing Hormone Release.
Journal of Neuroscience, 2013; 33 (49): 19051 DOI: 10.1523/JNEUROSCI.3878-13.2013

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