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

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $532,401

## Abstract

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 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:** 10049123
- **Project number:** 1R01DK123098-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Pingwen Xu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $532,401
- **Award type:** 1
- **Project period:** 2020-09-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10049123

## Citation

> US National Institutes of Health, RePORTER application 10049123, Testosterone and estrogen signaling pathways in the medial amygdala interact to control energy homeostasis (1R01DK123098-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10049123. Licensed CC0.

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