Estrogen's Rapid Action Triggers Binge Drinking in Females

Females "pregame," meaning they drink large amounts of alcohol within the first half hour after it's offered because the hormone estrogen influences binge drinking. For what is believed to be the first time, the study shows that estrogen increases binge drinking in females and helps explain the differences in alcohol consumption between men and women. The majority of research on alcohol consumption has been conducted on male individuals, which has led to a lack of knowledge about the variables affecting female alcohol-drinking behavior(1^✔ ✔Trusted Source
Preclinical Study Finds Surges in Estrogen Promote Binge Drinking in Females

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It is acknowledged, however, that women are more likely than men to overindulge and are therefore more susceptible to the negative health consequences of alcohol.

Women increased their heavy alcohol consumption more than males during the pandemic lockdown. Dr Pleil stated that this habit has significant health implications for women "because numerous studies demonstrate this pattern of drinking exacerbates the negative effects of alcohol."

During the pandemic and in the years that followed, women experienced significantly more hospitalizations and problems due to alcohol than males.

Peak Levels of Estrogen Associated with Increased Alcohol Consumption

In a 2021 study, Dr. Pleil and her team showed that a specific subpopulation of neurons in a brain region called the bed nucleus of the stria terminalis (BNST) was more excitable in female mice than in males. This enhanced activity correlated with their binge drinking behavior.

But what makes this neural circuit more excitable in females? “Estrogen has such powerful effects on so many behaviors, particularly in females,” Dr. Pleil said. “So, it makes sense that it would also modulate drinking.”

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To assess estrogen’s potential involvement, the researchers, including first author Dr. Lia Zallar, who was a graduate student in the Pleil lab at the time of the research, began by monitoring the hormone levels throughout the oestrous cycle of female mice. Then, they served up the alcohol. They found that when a female has a high level of circulating estrogen, she drinks much more than on days when her estrogen is low.

That enhanced bingeing behavior was reflected in heightened activity in those same neurons in the BNST. “When a female takes her first sip from the bottle containing alcohol, those neurons go crazy,” Dr. Pleil said.

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“And if she’s in a high-estrogen state, they go even crazier.” That extra boost of neural activity means the mice hit the bottle even harder, particularly within the first 30 minutes after the alcohol was made available, a behavior Dr. Pleil refers to as “front-loading.”

Surprising Discovery: Cell-surface Receptors Allow Estrogen to Act Fast

Although the researchers suspected estrogen would have an effect on drinking, they were surprised by its mechanism of action. This steroid hormone typically regulates behaviors by binding to receptors that then travel to the nucleus, where they alter the activity of specific genes—a process that could take hours.

However, Dr. Pleil and her team realized that something else must be happening when estrogen infused directly into the BNST excited the neurons and triggered binge drinking within minutes.

So, the researchers tested estrogen that had been doctored so it could not enter cells and bind to nuclear receptors—a feat of chemical engineering performed by Dr. Jacob Geri, assistant professor of pharmacology at Weill Cornell Medicine.

They determined that when estrogen promotes bingeing, the hormone binds to receptors on the neurons’ surface, where it directly modulates cell-cell communication.

“We believe this is the first time that anybody has shown that during a normal oestrous cycle, endogenous estrogen made by the ovaries can use such a rapid mechanism to control behavior,” Dr. Pleil said. That rapid action drives the front-loading of alcohol when estrogen is high.

The team identified the estrogen receptor that mediates this effect and determined that it is expressed in the excited BNST neurons and in neurons from other brain regions that excite them. The researchers are now investigating the signaling mechanisms for this effect, and they will also examine whether the same system regulates drinking in males.

“All of the infrastructure is there in males, too: the estrogen receptors and the basic circuit organization,” Dr. Pleil said. The only difference will be the source of the estrogen, which in males without an ovarian source relies on the local conversion of testosterone to estrogen in the brain.

Inhibiting the enzyme that synthesizes estrogens could offer a novel treatment for selectively reducing alcohol consumption when hormone levels surge. An FDA-approved version of such an inhibitor is currently used to treat women with estrogen-sensitive cancers.

“Combining this drug with compounds that modulate the downstream effects of the chemicals produced by the BNST neurons could potentially provide a new, targeted approach for treating alcohol use disorder,” Dr. Pleil said.

Reference:

1. Preclinical Study Finds Surges in Estrogen Promote Binge Drinking in Females- (https:news.weill.cornell.edu/news/2024/12/preclinical-study-finds-surges-in-estrogen-promote-binge-drinking-in-females)

Source-Eurekalert