ABSTRACT
Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome characterized by persistent anovulation, oligomenorrhea or amenorrhea, and hyperandrogenism, in the absence of thyroid, pituitary, and/or adrenal disease. At the level of the ovary, there are recruitment and growth of follicles to the small antral stage, with no selection of a dominant, preovulatory follicle. This leads to the accumulation of multiple, small, antral follicles, which give the syndrome its name.1-3 There is also evidence of hyperfunctioning of the thecal compartment in addition to the relative hypofunctioning of the granulosa. While many women with PCOS have relatively high circulating levels of luteinizing hormone (LH) compared with folliclestimulating hormone (FSH), this is not so in all women and does not account totally for the observed increase in thecal production of androgens or the relative quiescence and FSH resistance of the granulosa. This complex disorder probably has its origins within, as well as outside, the hypothalamic-pituitary-ovarian axis. Clinical and basic research have highlighted the roles, within the reproductive tract,
neuroendocrine, and also endocrine regulators probably contribute to the pathogenesis of this disorder.4-6 This chapter describes what is currently known about the ovarian insulin-like growth factor (IGF) system in normal follicle development and in PCOS. The focus is on insulin-like peptides, since the IGF family integrates endocrine and metabolic axes relevant to PCOS and the intraovarian IGF system may play a role in hyperandrogenemia and the arrest of follicular development observed in this disorder.7-10
INSULIN-LIKE GROWTH FACTOR SYSTEM
The IGF system comprises IGF peptides, IGF receptors, a family of high-affinity IGF binding proteins (IGFBPs), a family of IGFBP-related proteins, and a family of IGFBP proteases.11-13 It is one of the most extensively studied systems in the ovary.10 Both IGF-I and IGF-II are small, mitogenic and differentiative peptides that have insulin-like metabolic effects mediated upon binding to specific high-affinity membrane
growth hormone IGF-I is also known as somatomedin C, and IGF-II has been classically viewed as a tumorigenic factor and a fetal growth factor. The IGF type I receptor is a typical growth factor receptor with signal transduction mediated via the tyrosine kinase pathway.14
