# Testosterone and estrogen signaling pathways in the medial amygdala interact to control energy homeostasis

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $64,587

## Abstract

A. Abstract of Parent Grant
Sex steroids, including estrogens and androgens, play an important role in regulating energy homeostasis. Brain sex steroid
signaling is required for normal body weight maintenance. We previously showed that estrogen receptor α (ERα) neurons
in the medial amygdala (MeA) stimulate physical activity and energy expenditure to decrease body weight in both males
and females. It suggests that the estrogen/ERαMeA circuit constitutes part of a previously undefined brain metabolic
signaling in both males and females. Interestingly, the MeA has high levels of other three key components of
testosterone/estrogen signaling, including an essential enzyme for estrogen synthesis (aromatase; Aro), and key mediating
receptors for testosterone/estrogen signaling (androgen receptor, estrogen receptor α and β; AR, ERα and ERβ). These
data raise the possibility that circulating testosterone directly binds to AR or is aromatized by Aro to estradiol, which then
binds to ERα or ERβ to exert metabolic functions. We hypothesize that the neurosteroid testosterone/estrogen signaling
pathways in the MeA interact to maintain normal energy homeostasis. To test this, three mutant mice will be generated
to have each of these three components deleted specifically in the MeA neurons, respectively. These mouse strains (both
males and females) will be used to determine the physiological roles of these three components in maintaining energy
homeostasis in different sexes. The functional interactions between these components and the sex hormones will also be
examined. Results from these studies will advance our current understanding of body weight control and the development
of obesity in general. Further, our studies may narrow down the specific brain regions and hormone/receptors that are
critical for the regulation of energy balance, which may serve as targets for the development of new anti-obesity
strategies.

## Key facts

- **NIH application ID:** 10632260
- **Project number:** 3R01DK123098-03S1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Pingwen Xu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $64,587
- **Award type:** 3
- **Project period:** 2020-09-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10632260

## Citation

> US National Institutes of Health, RePORTER application 10632260, Testosterone and estrogen signaling pathways in the medial amygdala interact to control energy homeostasis (3R01DK123098-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10632260. Licensed CC0.

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