# Androgen Excess Causes Adipogenic Dysfunction in PCOS Women

> **NIH NIH P50** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $273,757

## Abstract

PROJECT SUMMARY/ABSTRACT
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder of women characterized by androgen
excess, menstrual irregularity and polycystic ovaries. Affecting 6-10% of reproductive-aged women, 60–95% of
PCOS women have insulin resistance that is exaggerated by increased total and abdominal fat deposition,
predisposing to metabolic syndrome and diabetes as risk factors for cardiovascular disease (CVD). Of
concern, androgen excess in PCOS women who are normal-weight is closely linked with preferential
abdominal fat deposition and increased intra-abdominal fat mass that is positively correlated with serum fasting
insulin and lipid levels. Moreover, androgen excess in these PCOS women also is accompanied by a greater
proportion of small adipocytes (fat cells) in subcutaneous (SC) abdominal adipose where fat is normally
stored. Therefore, normal-weight PCOS women may have a reduced capacity of SC adipose to safely store
fat. When energy intake exceeds that capacity, SC abdominal adipocytes may overfill with lipid and promote
excess lipid deposition in abnormal (ectopic) locations, where increased oxidative stress underlies metabolic
dysfunction (i.e., lipotoxicity). We hypothesize that androgen excess in normal-weight PCOS women alters SC
abdominal adipogenesis, defined as the ability of adipose stem cells to develop into mature adipocytes and, in
doing so, impairs metabolic function. Further, these androgen actions may originate from heritable changes in
the genes of these stem cells or their developing adipocytes without affecting the DNA sequence of the genes
themselves (i.e. epigenetic). In this NCTRI Project IV renewal, we will 1) examine molecular mechanisms of
SC abdominal adipogenesis in normal-weight PCOS women compared to weight- and age-matched
normoandrogenic ovulatory women (controls), 2) determine the role of androgen action in SC abdominal stem
cell dysfunction and its relationship to metabolism in these PCOS women receiving the antiandrogen, flutamide
or placebo through a clinical trial and 3) identify crucial epigenetic changes that distinguish SC abdominal stem
cells in such PCOS women compared to those of weight- and age-matched control women. Understanding
androgen action during SC abdominal adipogenesis in normal-weight PCOS women and its adverse effects on
metabolic function through stem cell differentiation allows development of new and personalized clinical
strategies, including stem cell therapies and pharmacological interventions, that could improve metabolic
function in PCOS women and decrease their susceptibility to CVD.

## Key facts

- **NIH application ID:** 10136654
- **Project number:** 5P50HD071836-09
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Daniel A Dumesic
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $273,757
- **Award type:** 5
- **Project period:** 2013-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136654

## Citation

> US National Institutes of Health, RePORTER application 10136654, Androgen Excess Causes Adipogenic Dysfunction in PCOS Women (5P50HD071836-09). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10136654. Licensed CC0.

---

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