415. Increased expression of an androgen receptor regulated gene, kit ligand, in polycystic ovaries

Abstract

Polycystic ovaries (PCO) are induced by pathological or pharmacological female androgen excess, but the role of the androgen receptor (AR) in the pathogenesis of PCO is unknown. We therefore tested the hypothesis that PCO have increased expression of AR or kit ligand (KITL), a cytokine that was recently identified as a candidate AR-regulated gene in the ovary (1). Immunohistochemical analysis of AR and KITL expression was performed on archival paraffin-embedded sections of 8 morphologically normal and 8 polycystic ovaries from women under the age of 40 years. Stained sections were scanned with a NanoZoomer Digital Pathology System and immunoreactivity was qualitatively assessed using a 0-3+ scale, where 3+ represents the most intense staining. Electronic images of follicles at different stages of folliculogenesis were assessed by two independent observers who were blinded to the morphology of the source ovary. Each individual ovary contributed a minimum of 1 follicle per size class and a minimum of 10 follicles per size class were analysed. AR immunoreactivity was present in granulosa cells at all stages of folliculogenesis, in thecal cells of large antral follicles, and in the ovarian stroma. Staining intensity for AR did not differ between normal and polycystic ovaries. KITL expression, summarised in Table 1, was found to be significantly elevated in the oocytes of primordial and primary follicles and in the granulosa cells of follicles at all stages of folliculogenesis. These results show that AR expression is normal in PCO but expression of an AR-regulated gene is increased, potentially due to an excess of androgen hormone that is characteristic of women with PCO. Based on the roles of KITL established by murine studies, increased expression of KITL could explain many of the features of PCO including follicle excess, hyperthecosis and abnormal androgen secretion.