title: Inflammation in Polycystic Ovary Syndrome: underpinning of insulin resistance and ovarian dysfunction.
abstract: Chronic low-grade inflammation has emerged as a key contributor to the pathogenesis of Polycystic Ovary Syndrome (PCOS). A dietary trigger such as glucose is capable of inciting oxidative stress and an inflammatory response from mononuclear cells (MNC) of women with PCOS, and this phenomenon is independent of obesity. This is important because MNC-derived macrophages are the primary source of cytokine production in excess adipose tissue, and also promote adipocyte cytokine production in a paracrine fashion. The proinflammatory cytokine tumor necrosis factor-α (TNFα) is a known mediator of insulin resistance. Glucose-stimulated TNFα release from MNC along with molecular markers of inflammation are associated with insulin resistance in PCOS. Hyperandrogenism is capable of activating MNC in the fasting state, thereby increasing MNC sensitivity to glucose; and this may be a potential mechanism for promoting diet-induced inflammation in PCOS. Increased abdominal adiposity is prevalent across all weight classes in PCOS, and this inflamed adipose tissue contributes to the inflammatory load in the disorder. Nevertheless, glucose ingestion incites oxidative stress in normal weight women with PCOS even in the absence of increased abdominal adiposity. In PCOS, markers of oxidative stress and inflammation are highly correlated with circulating androgens. Chronic suppression of ovarian androgen production does not ameliorate inflammation in normal weight women with the disorder. Furthermore, in vitro studies have demonstrated the ability of pro-inflammatory stimuli to upregulate the ovarian theca cell steroidogenic enzyme responsible for androgen production. These findings support the contention that inflammation directly stimulates the polycystic ovary to produce androgens.
authors.affiliation: Indiana University School of Medicine, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Indianapolis, IN 46202, USA. gonzalef@iupui.edu
authors.forename: Frank
authors.initials: F
authors.lastname: González
mesh_terms: D000818:Animals; D004032:Diet / Q000009:adverse effects; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications; D007333:Insulin Resistance; D010053:Ovary / Q000503:physiopathology*; D011085:Polycystic Ovary Syndrome / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*