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New research suggests the conversion of testosterone to estrogen in the brain is crucial for male sexual desire

Scientists have uncovered an enzyme that appears to play a key role in regulating sexual behavior in males. Their new research, published in the journal Endocrinology, found that selectively disrupting the enzyme aromatase in the brains of male mice led to a sharp decrease in sexual behavior.

“Over the past 30 years, we have been interested in various roles of aromatase, the enzyme that produces estrogen from testosterone locally in a number of body sites including the brain,” explained Serdar Bulun, the chair of obstetrics and gynecology at Northwestern University Feinberg School of Medicine and Northwestern Medicine.

“There have been a number of reports about the function of aromatase in specific brain regions for sexually dimorphic brain development particularly in males during fetal development and early postnatal life; and sparse data also suggested that the aromatization of testosterone to estrogen in the brain might play a role in regulating libido, but this remained as an important question in the adult male.”

“There was a definitive way to answer this question: to knock out aromatase selectively in the brain and find out if sexual activity or desire changes. This is what we did,” Bulun said.

The researchers found that sexual activity in male mice decreased by 50% when they knocked out a single gene responsible for encoding the enzyme, despite the mice having higher levels of blood testosterone levels (compared with control male mice).

Normally, if a male mouse is put with a female one, Bulun said in a news release, “it would chase after her and try to have sex with her. If you knock out the aromatase gene in the brain, their sexual activity is significantly reduced. There is less frequency of mating. The male mice are not that interested.”

The decreased sexual behavior in male mice was fully restored after the systemic administration of both estradiol and testosterone — but not by estradiol or testosterone alone. This indicates that the conversion of testosterone to estrogen in the brain plays an important role in male sexual behavior, the researchers said.

“Estrogen and testosterone have been traditionally labeled as ‘female’ and ‘male’ sex steroids, respectively. Our findings underscore that this is a superficial characterization. Both steroids serve important roles in both sexes,” Bulun told PsyPost.

“Testosterone in the brain serves two purposes for sexual desire. As an androgen, it stimulates it. As a further twist, testosterone is also aromatized and thus serves as a precursor for estrogen in the brain.”

“This additional estrogenic effect in the brain is necessary for achieving full sexual desire. Because males (versus females) have enormously higher levels of blood testosterone, they can concentrate estrogen in certain brain regions much more effectively compared with females. We hope that our findings will help design treatments for the disorders involving sexual desire,” Bulun said.

But the researchers still have more to learn about the relationship between aromatase and sexual behavior.

“We knocked out aromatase in the entire brain. Aromatase in the adult brain is present in specific locations such as the hypothalamus, amygdala and several other regions. We still need to pinpoint the microscopic brain regions responsible for controlling libido via more refined conditional knockout technology,” Bulun explained.

“There also remain other key questions. How does estrogen regulate sexual desire? What are the downstream neurotransmitters that mediate this estrogenic effect? How do aromatase-intense regions communicate with the cortex to regulate sexual activity?”

The study, “Brain Aromatase and the Regulation of Sexual Activity in Male Mice“, was authored by David C. Brooks, John S. Coon V., Cihangir M. Ercan, Xia Xu, Hongxin Dong, Jon E. Levine, Serdar E. Bulun, and Hong Zhao.



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