# Dissecting Effects of Estrogen Deficiency on Satellite Cells and Muscle Regeneration in Females and Males

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $486,409

## Abstract

Skeletal muscle is repetitively injured throughout life and requires continual regeneration. The
ability of skeletal muscle to regenerate declines significantly with age, although the specific
factors that govern this decline are poorly understood. One key systemic factor that declines
with age in females is the sex hormone, estradiol (E2). We have discovered that experimental
manipulation of both E2 levels and that of its receptor ERα specifically in satellite cells of young
adult females leads to decrement in satellite cell pool size and decline in regenerative potential.
This project seeks to understand the mechanisms by which these effects are mediated in
females, probes the sex-specific nature of this regulation, and investigates interventions in aged
mice. We will elucidate the molecular and cellular regenerative details mediated by estradiol and
importantly the functional outcomes on muscle contraction. Driven by our robust preliminary
data, we will test the overarching hypothesis that E2 is the primary sex hormone regulating
skeletal muscle maintenance through estrogen receptor-mediated mechanisms in
satellite cells. In Aim 1 we design experiments to probe the cellular physiological
consequences of the E2-ERα signaling axis in satellite cells. Aim 2 focuses on estrogenic
mechanisms regulating satellite cells and muscle regeneration of males, testing the provocative
hypothesis that E2 plays a significant role in males as well as females. In Aim 3 we will
interrogate responsiveness of satellite cells in aged mice to E2 and a new, third generation
selective estrogen receptor modulator, bazedoxifene (BZA), which we have shown to be an
estrogen receptor agonist in satellite cells. Within each of the three primary aims we utilize state
of the art transcriptional and chromatin profiling approaches to gain insight into signaling
pathways, for example, that are similar (or distinct) between satellite cells from females and
males when sex hormones or receptors are manipulated. At the completion of this project we
will know in molecular detail how E2 contributes to overall skeletal muscle health through
hormone receptor mediated-mechanisms specifically in satellite cells. Women spend one-third
of their life in an E2-deficient state and androgen (and thus potential estrogenic effects mediated
by aromatase) declines in males with age. As the aging population continues to increase it
becomes increasingly important that the impact of this biological variable on skeletal muscle
health be understood.

## Key facts

- **NIH application ID:** 10174678
- **Project number:** 5R01AG062899-03
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Michael Kyba
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $486,409
- **Award type:** 5
- **Project period:** 2019-09-30 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174678

## Citation

> US National Institutes of Health, RePORTER application 10174678, Dissecting Effects of Estrogen Deficiency on Satellite Cells and Muscle Regeneration in Females and Males (5R01AG062899-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10174678. Licensed CC0.

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