Key points:
- Researchers have discovered a feedback loop involving estrogen that may make women more prone to nicotine addiction than men.
- Estrogen induces the expression of olfactomedins, proteins that are suppressed by nicotine in key areas of the brain involved in reward and addiction.
- The findings suggest that estrogen–nicotine–olfactomedin interactions could be targeted with therapies to help control consumption.
A newly discovered feedback loop involving estrogen may explain why women are more likely to become dependent on nicotine faster and with less exposure than men. The research could lead to new treatments for women who are having trouble quitting nicotine-containing products.
For the study, recently presented at the annual meeting of the American Society for Biochemistry and Molecular Biology, the researchers used large sequencing datasets of estrogen-induced genes to identify those that are expressed in the brain and exhibit a hormone function. They found just one class of genes that met these criteria: those coding for olfactomedins.
The team then performed a series of studies with human uterine cells and rats to better understand the interactions between olfactomedins, estrogen and nicotine. The results suggested that estrogen activation of olfactomedins—which is suppressed when nicotine is present—might serve as a feedback loop for driving nicotine addiction processes by activating areas of the brain’s reward circuitry, such as the nucleus accumbens.
The researchers are now working to replicate their findings and definitively determine the role of estrogen. This knowledge could be useful for those taking estrogen in the form of oral contraceptives or hormone replacement therapy, which might increase the risk of developing a nicotine use disorder.
“Our research has the potential to better the lives and health of women struggling with substance use,” she said. “If we can confirm that estrogen drives nicotine seeking and consumption through olfactomedins, we can design drugs that might block that effect by targeting the altered pathways. These drugs would hopefully make it easier for women to quit nicotine.”
The team also wants to determine the exact olfactomedin-regulated signaling pathways that drive nicotine consumption and plan to conduct behavioral animal studies to find out how manipulation of the feedback loop affects nicotine consumption.