# Role of Melanin-concentrating Hormone in the Integration of Sleep and Reproductive Physiology

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $35,275

## Abstract

Project Summary/Abstract
Reduced and fragmented sleep is associated with infertility in humans. Nearly one fifth of American couples
struggle with infertility and, with increasing environmental exposure to sleep and circadian disruptors,
deficiencies in pubertal development and fertility will likely continue to increase. At the apex of the hypothalamo-
pituitary-gonadal (HPG) axis, central to reproductive physiology, are gonadotropin-releasing hormone (GnRH)
neurons. Episodic release of GnRH drives pulsatile secretion of luteinizing hormone (LH) and follicle-stimulating
hormone (FSH), which in turn act on the gonads to promote maturation of gametes and production of sex
steroids. A bout of high-frequency LH pulses is required for both pubertal onset and ovulation. Notably, the rise
in LH pulse frequency that precipitates puberty occurs during sleep, while in adults, LH pulse frequency is
reduced during sleep. However, the mechanisms linking sleep and reproduction represent a significant gap in
the literature. We hypothesize that hypothalamic melanin-concentrating hormone (MCH) neurons temporally
integrate the activity of the sleep and reproductive systems. MCH neurons are active during sleep and have
projections to areas of reproductive control. Furthermore, administration of MCH to the medial preoptic area
(mPOA), where GnRH neurons are abundant, is capable of both increasing and suppressing LH pulsatility. One
possible explanation for this is that MCH neurons and their targets are more heterogeneous than previously
thought, particularly between the sexes. Additionally, variability of sleep patterns and response to sex steroid
feedback throughout the female estrous cycle are not accounted for in a consistent manner across studies. We
aim to define the projection targets and co-expressed peptides of MCH neurons in the mouse brain to reveal
distinct subpopulations and any differences therein defined by sex or the estrogen milieu. Further, we aim to
systematically determine the effect of chemogenetically manipulating each of these subpopulations on cortical
EEG and blood LH concentration as outputs of sleep and HPG axis activation, respectively. These studies will
be performed in male and female mice in varied estrogen milieu and the results compared across groups. Finally,
using the same experimental groups, we will measure LH secretion following manipulation of MCH neuronal
subpopulations in both sleep and waking. This three-pronged approach will enable us to untangle the effects of
MCH on both sleep and the reproductive axis and, importantly, the novel question of how these roles are related.
Our attention to MCH neuronal subpopulations, sex differences, and the effects of the sex steroid milieu on both
sleep and the HPG axis will define the transcriptional and functional heterogeneity of MCH neurons and
contribute to a working model of how sleep and the HPG axis interact to result in normal pubertal development
and reproduction.

## Key facts

- **NIH application ID:** 10430217
- **Project number:** 5F31HD102160-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Bethany Genelle Beekly
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $35,275
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-04-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10430217

## Citation

> US National Institutes of Health, RePORTER application 10430217, Role of Melanin-concentrating Hormone in the Integration of Sleep and Reproductive Physiology (5F31HD102160-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10430217. Licensed CC0.

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