# A role for hypothalamic melanocortin 3 receptors in integrating energy state with reproductive physiology

> **NIH NIH F32** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $38,580

## Abstract

Proposal Summary:
To assure adequate energy resources for the energetically demanding process of reproduction, central
reproductive physiology is influenced by hormonal and neural signals of energy balance. As a result,
maladaptive changes in energy homeostasis in either the positive or negative direction can exert dramatic
effects on reproductive success and fertility. For example, both anorexia nervosa and obesity are associated
with an increased likelihood for reproductive disorders or infertility. Despite the importance of physiological
interactions between metabolic state and reproduction, the underlying mechanisms and neural pathways
linking metabolism and reproduction are not fully understood. One key pathway connecting metabolism and
reproduction is the central melanocortin system. Previous studies have determined that alpha melanocyte
stimulating hormone (α-MSH), agouti related protein (AgRP), and melanocortin 4 receptor (MC4R) modulate
multiple aspects of reproductive function. Here, we provide data demonstrating that the melanocortin-3
receptor (MC3R) plays critical, bidirectional roles in integration of energy and reproductive states. We show
defects in the hypothalamic-pituitary-gonadal axis, as well as defects in energy homeostasis in response to
reproductive state in MC3R KO mice. Therefore, the current proposal will characterize the anatomical,
physiological, and behavioral role of the MC3R in reproductive function. We will first map the anatomical
distribution of the MC3R within hypothalamic reproductive circuitry. Subsequent electrophysiological assays
will be performed to determine how the MC3R modulates the cellular physiology of the central reproductive
neural circuitry located in the hypothalamus. Finally, we will utilize a combination of genetic, pharmacological,
and DREADD (designer receptors exclusively activated by designer drugs) assays to determine the contribution
of the MC3R to hypothalamic-pituitary-gonadal axis function and reproductive physiology. Overall, this
proposal will provide a holistic view of the behavioral, physiological, and mechanistic functions of the MC3R in
mediating interactions between reproductive function and energy homeostasis, potentially providing novel
therapeutic strategies for infertility in the increasing obese and anorexic populations.

## Key facts

- **NIH application ID:** 9870943
- **Project number:** 5F32HD095620-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Patrick Sweeney
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $38,580
- **Award type:** 5
- **Project period:** 2018-03-01 → 2020-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870943

## Citation

> US National Institutes of Health, RePORTER application 9870943, A role for hypothalamic melanocortin 3 receptors in integrating energy state with reproductive physiology (5F32HD095620-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9870943. Licensed CC0.

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