Jessica George ’24

Figure 1 Nicotine use disorder has a profound impact on hormones, yet sex differences are poorly understood.

Maintaining a harmonious sex-hormone balance is essential for the optimal functioning of the body, as it regulates a wide range of physiological processes. Aromatase serves as the critical enzyme responsible for the conversion of androgens into estrogens, a process fundamental to functions associated with emotional and cognitive regulation. Nicotine use disorder has a profound impact on hormones, yet sex differences are poorly understood. Research conducted by Manin Dubol and colleagues from Uppsala University provides a comprehensive examination of the immediate impact of nicotine exposure on the enzymatic activity of aromatase within the limbic brain regions of healthy female subjects. 

This investigation recruited ten healthy women aged 22-33 from Uppsala University Hospital. All women revealed no neurological disease, psychiatric disorders, high blood pressure, pregnancy, hormonal/psychoactive drug treatment, or hormonal contraceptive use. To begin, venous blood samples were collected and PET scans with [11C]cetrozole were taken from each of the participants in order to measure baseline levels of androgen and estrogen and measurements of aromatase activity, respectively. For each participant, the next session was administered one menstrual cycle away to ensure similar hormone levels. This is vital as hormones fluctuate during the menstrual cycle and it may interfere with the results if both samples were taken at different baseline hormone levels. At the second session, 0.5mg of nicorette nasal spray was administered to the participants and a second round of blood samples and PET scan were taken. Nasal administration was used as it provides fast delivery to the brain. 

Neuroimaging and blood sample analysis revealed a decrease in aromatase availability after administration of the nasal nicotine. PET scans revealed that the highest amounts of aromatase were found in the thalamus. High levels were also found in the amygdala and hypothalamus. When nicotine was administered, there was a reduction in aromatase availability, determined by graphical observation of [11C]cetrozole volume distribution, in those three areas. It is hypothesized that nicotine molecules serve as a competitive inhibitor of aromatase, blocking it from its activity. The implications of these findings are substantial to the neuroscience and women’s health community. By elucidating the link between nicotine and aromatase activity in the limbic brain, this research brings to light the potential mechanisms underlying the relationship between smoking and mood disorders, which are often more prevalent in women. This study hints at a mechanism through which nicotine’s causes mood disturbances seen in smokers and opens gates for potential therapeutic/medical targets.

Citations: 

1. M. Dubol, J. Immenschuh, M. Jonasson, et. al. Acute nicotine exposure blocks aromatase in the limbic brain of healthy women: A [11C]cetrozole PET study. Comprehensive Psychiatry 123, (2023) https://doi.org/10.1016/j.comppsych.2023.152381. 
2. Image retrieved from:  https://www.pickpik.com/cigarette-tobacco-kills-nicotine-cigar-joint-4881