Proteomics and genomics: A hypothesis-free approach to the study of the role of visceral adiposity in the pathogenesis of the polycystic ovary syndrome

The polycystic ovary syndrome (PCOS) is possibly the most common endocrine disorder in premenopausal women. The primary defect in PCOS consists of an exaggerated androgen secretion by the ovaries and the adrenal glands of affected women, which is amplified by several mechanisms including abdominal adiposity and insulin resistance. Abdominal adiposity contributes to hyperandrogenism by favoring insulin resistance and compensatory hyperinsulinism, because insulin facilitates ovarian and adrenal androgen synthesis, among other mechanisms. Furthermore, mounting evidence suggest that androgen excess may also contribute to a predominantly abdominal disposition of body fat in women, suggesting that women with PCOS suffer from a vicious circle whereby androgen excess favoring the abdominal deposition of fat further facilitates androgen secretion by the ovaries and adrenals. Familial aggregation of PCOS cases suggests an inherited component in PCOS, yet the genetic mechanisms underlying this inheritance remain elusive. The present manuscript reviews the hypothesis-free approaches - such as genomics and proteomics - that have been used recently to study PCOS, focusing on studies from our group addressing the gene expression profiles and the proteome of visceral adipose tissue of morbidly obese women presenting with or without PCOS.