Androgen actions in metabolic tissues in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common reproductive disorder characterized by irregular ovulation, cyst-like follicles on the ovaries, and hyperandrogenism. PCOS is also strongly associated with increased risk of obesity and metabolic diseases such as type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). Hyperandrogenism independently associates with many of the metabolic symptoms observed in women with PCOS, and increased androgen signaling in the female brain is hypothesized to impair central homeostatic mechanisms controlling food intake and body weight. However, peripheral metabolic organs such as pancreas, liver, fat, and skeletal muscle all express the androgen receptor, suggesting that direct androgen signaling in these organs may disrupt peripheral metabolic health. Although it is difficult to separate the impacts of hyperandrogenism from hyperinsulinemia and insulin resistance, tissue explant studies and transgenic knockout models provide the ability to interrogate signaling through the androgen receptor in metabolic organs. This review will summarize and discuss recent evidence implicating hyperandrogenism as a driver of metabolic impairments in PCOS, with an emphasis on the molecular mechanisms by which androgens may alter metabolic function in the periphery in females.