# Melanocortin 3 receptor in neural circuits linking reproductive state and metabolism

> **NIH NIH F32** · VANDERBILT UNIVERSITY · 2021 · $66,390

## Abstract

PROJECT SUMMARY
Neural circuits modulating metabolic state and reproduction must communicate with each other to maintain
homeostasis. Despite an increasing prevalence of both metabolic and reproductive disorders, our
understanding of neural circuitry linking energy homeostasis and reproduction remains rudimentary.
Melanocortin 3 receptor (MC3R) is ideally positioned, both anatomically and functionally, to mediate direct
communication between reproductive and metabolic circuits. MC3R is expressed in multiple areas of the brain,
including the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus of the hypothalamus
(ARH). The AVPV and ARH are critical sites controlling reproduction and energy balance, and they are linked
by direct neural connections. Therefore, MC3R-expressing neurons in the AVPV and ARH may represent
important components of a core neural circuit that functions to integrate the neural control of energy balance
and reproductive state. However, the cellular identity of MC3R-expressing neurons in the AVPV and ARH has
not been determined, nor has the organization of their neural projections been defined. Recent evidence
suggests MC3R may also functionally mediate the exchange of information between metabolic and
reproductive state. During metabolic challenges resulting from reproductive state, such as pregnancy and
ovariectomy, deletion of MC3R results in mice gaining too little weight or too much weight, respectively.
Deletion of MC3R results in additional reproductive and metabolic disturbances in males and females,
including adverse responses to fasting, disruptions to feeding behavior, and altered circulating hormone
concentrations. Moreover, females with MC3R mutations typically exhibit more aberrant reproductive and
metabolic phenotypes, compared with those observed in mutant males. However, a detailed understanding of
the mechanisms causing these differential responses in males and females is lacking. Because sex steroids
specify the organization of sexually dimorphic neural circuits during critical periods of development, it is
possible that exposure to estrogen during these periods may cause permanent changes in the architecture of
MC3R regulated circuits, and consequently, reproductive and metabolic physiology. The overall hypothesis of
this application is that MC3R neurons provide a neurological substrate for integration of metabolic signals with
reproductive status, and that this circuit may be configured differently in males and females. As a first step
toward testing this hypothesis, the following two specific aims will be pursued: 1) Define the molecular
phenotypes of neurons that express MC3R in the AVPV and ARH of male and female mice, and map the
organization of their neural projections; 2) Determine if the organization and function of MC3R circuits depends
upon estrogen receptor signaling during postnatal development. Completion of these aims will establish a
novel framework for understanding neurologi...

## Key facts

- **NIH application ID:** 10102117
- **Project number:** 5F32DK123879-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Michelle Bedenbaugh
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $66,390
- **Award type:** 5
- **Project period:** 2020-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10102117

## Citation

> US National Institutes of Health, RePORTER application 10102117, Melanocortin 3 receptor in neural circuits linking reproductive state and metabolism (5F32DK123879-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10102117. Licensed CC0.

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