# A reciprocal relationship between alcohol and the p450 enzyme aromatase

> **NIH NIH F31** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $46,036

## Abstract

Project Summary
Excessive alcohol consumption is a significant problem in our society that causes far-reaching health, economic,
and personal issues. The steroid hormone estrogen (17β-estradiol; E2) is synthesized in organs throughout the
body, including the brain, via the conversion of testosterone into E2 by the cytochrome p450 enzyme aromatase
(AROM). E2 made in the ovaries has been shown to increase reward sensitivity, learning, and alcohol
consumption. In addition, there is clinical evidence that chronic alcohol consumption may upregulate AROM
activity and E2 synthesis, suggesting that additional sources of AROM may contribute to alcohol-related
behavior. I find that acute pharmacological AROM inhibition reduces alcohol drinking in males following 3 weekly
cycles of binge drinking and in females following 10 cycles. The bed nucleus of the stria terminalis (BNST), a
brain region highly associated with reward, anxiety, and addiction, is a known source of E2 receptor expression
and E2 transmission. Our laboratory has found that E2 administration to the BNST increases binge alcohol
consumption and increases glutamate release onto BNST corticotropin releasing factor (CRF) neurons. The
overarching hypothesis of this proposal is that there is a reciprocal relationship between alcohol and AROM,
such that alcohol drinking recruits increased AROM expression, resulting in increased E2 tone in the BNST that
promotes further binge alcohol consumption. I have developed a comprehensive research plan to address the
scientific questions derived from this hypothesis. In Aim 1, I will execute electrophysiological and behavioral
techniques to examine whether alcohol-induced E2 acts in the BNST to promote drinking. In Aim 2, I will
determine sites of increased AROM in the brain and body and evaluate their roles in binge drinking behavior
using electrophysiological, molecular, genetic, and behavioral techniques. The proposed work seeks to provide
information on the mechanisms driving binge alcohol consumption and has significant implications for the
widespread public health issue of excessive alcohol drinking.

## Key facts

- **NIH application ID:** 10386167
- **Project number:** 1F31AA029293-01A1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Lia Juliet Zallar
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-09-30 → 2024-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10386167

## Citation

> US National Institutes of Health, RePORTER application 10386167, A reciprocal relationship between alcohol and the p450 enzyme aromatase (1F31AA029293-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10386167. Licensed CC0.

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