# A cross-sectional exploratory study of rat sarcoma (Ras) activation in non-obese women with and without polycystic ovary syndrome

## TL;DR

This study explores Ras signaling proteins in non-obese women with and without PCOS to understand differences in growth factors and signaling pathways.

## Contribution

The study identifies specific proteins with altered levels in non-obese PCOS, suggesting compensatory angiogenesis.

## Key findings

- PCOS women had higher free androgen index and anti-Müllerian hormone levels.
- VEGFA and EGFR were increased, while EGFR1 was decreased in PCOS.
- Altered signaling suggests compensatory angiogenesis in a dysfunctional endothelial environment.

## Abstract

Studies in obese polycystic ovary syndrome (PCOS) have shown growth factors that activate rat sarcoma (Ras) proteins, which regulate intracellular signaling pathways, differ in PCOS; however, it is difficult to account for obesity, insulin resistance, and systemic inflammation that are linked to many of the features found in PCOS. This study explores Ras signaling proteins and related growth factors in non-obese women with and without PCOS. Somascan proteomic analysis of circulating KRas, Ras GTPase-activating protein-1 (RASA1), and 45 growth factor-related proteins that signal through Ras was undertaken in a non-obese population of women with (n=44) and without (n=78) PCOS, groups matched for age and body mass index (BMI), without insulin resistance (HOMA-IR) or systemic inflammation (normal CRP; C-reactive protein). There was an increase in the free androgen index (FAI, p<0.0001) and anti-Müllerian hormone (AMH, p<0.0001) in PCOS. Cohen's d showed a moderate effect size for 3 proteins, of which Vascular endothelial growth factor-A (VEGFA) and EGFR were increased and EGFR1 was decreased in PCOS (all FDR p<0.05). EGFR and VEGF pathways interact closely and when EGFR signaling decreases, VEGFA may increase to maintain angiogenic balance, suggesting that in non-obese PCOS there may be a signal for compensatory angiogenesis in a dysfunctional endothelial environment.

See also the graphical abstract(Fig. 1).