The role of intraovarian regulators in the aetiology of polycystic ovarian syndrome

Abstract

The present review demonstrates that the availability of bioactive FSH and LH in PCOS is normal and that granulosa cells of PCO are not apoptotic and instead hyperexpress functional FSH receptors and may possess intact aromatase activity. Consequently, these cells respond excessively to exogenous FSH stimulation and produce high amounts of oestradiol bothin vivoandin vitro. The altered developmental capacity of follicles from PCOin vivois most likely due to the abnormal follicular milieu of PCO and the culminating effects of intrafollicular inhibitors and stimulators. The failure of ovarian oestradiol production and follicular maturation to dominancein vivomay be due to a mechanism that interferes with the function of FSH, such as intraovarian steroids and growth factors. It has previously been shown that EGF and TGFα have inhibitory actions on follicular development, aromatization and LH receptor formation. In contrast, EGF enhances early follicular recruitment and growth. Therefore, it is hypothesized that EGF/TGFα may have a causal relationship in the mechanisms of anovulatory infertility in women with PCOS. Thus, an aberration in the regulation of follicular fluid EGF and/or TGFα may result in reduced numbers of granulosa cells, cessation of follicle selection and ultimately in the creation and maintenance of PCOS. The exact mechanism by which the hyperfunction of EGF/TGFα occurs and the trigger for this hyperactivity in the ovary remain to be determined. An experimental animal model may be required to assist such investigations in the future.