# Defining Sexual Dimorphism in the Skin

> **NIH NIH F31** · HARVARD MEDICAL SCHOOL · 2024 · $39,548

## Abstract

Defining Sexual Dimorphism in the Skin
 The skin executes many functions differently based on biological sex. Nevertheless, the cellular and
molecular mechanisms that give rise to these functional differences are poorly understood. Tissue-level sexual
dimorphism may be rooted in the behaviors of somatic stem cells, such as hair follicle stem cells, which maintain
tissues and can proliferate differently based on sex. This proposal will determine how biological sex, an
organismal-level characteristic, affects stem cell behavior. I will study sex differences in hair follicle renewal
during periods of both low and high sex hormones. Our preliminary data show that HFSCs, which regenerate
the hair follicle in a highly synchronized manner, exhibit different proliferative behaviors in male and female mice.
Before puberty, HFSCs begin to proliferate in males before females. This sexually dimorphic HFSC behavior
may be due to differences in sex hormones, sex chromosomes, or both. Conversely, after puberty, when sex
hormone production increases, HFSCs in females proliferate first. Distinct factors, therefore, may influence
HFSC sexual dimorphism at different stages of life. Before puberty, elimination of sex hormones by gonad
removal does not alter hair follicle renewal, suggesting circulating sex hormones do not establish sex differences
at this stage. In adulthood, we found that sex hormone depletion by gonad removal leads to dramatically
accelerated hair growth and eliminates sex differences. This accelerated hair follicle renewal is prevented in
gonadectomized males by treatment with the androgen 5𝛼-dihydrotestosterone. These data suggest that
androgens, a major type of sex hormone, can maintain HFSC quiescence after puberty. Cell-type specific
knockouts of the androgen receptor in HFSCs and the microenvironment, or niche, reveal that androgens
specifically maintain HFSC quiescence via the niche. My central hypothesis is prior to puberty, sex chromosomes
primarily govern HFSC sexual dimorphism. The rise of sex hormones in puberty masks these differences, and
androgens contribute to sex differences by altering the release of HFSC-modulating factors from the niche. I will
interrogate the determinants of HFSC sexual dimorphism using surgical and genetic mouse models, as well as
our expertise in constructing viral tools. In Aim 1, I will identify the contributions of sex chromosomes and sex
hormones to sexual dimorphism in juvenile HFSC behavior and upon puberty. Aim 2 will reveal the gene products
responsible for androgen-dependent HFSC quiescence using viral tools. Together, these data will identify the
foundations of sex differences in HFSCs. My findings may reveal novel avenues for development of treatments
for sexually dimorphic conditions.

## Key facts

- **NIH application ID:** 10993820
- **Project number:** 1F31AR083715-01A1
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Rebecca Jane Freeman
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $39,548
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10993820

## Citation

> US National Institutes of Health, RePORTER application 10993820, Defining Sexual Dimorphism in the Skin (1F31AR083715-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10993820. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*