Elevated endometrial androgen receptor expression in women with polycystic ovarian syndrome

Abstract

Androgen receptors (AR) have been identified in human endometrium; however, their role in endometrial cyclic development and function remains poorly understood. The objective of the present study was to investigate the profile of endometrial AR in normal menstrual cycles and in the endometrium of women with polycystic ovarian syndrome (PCOS). This syndrome is characterized by chronic hyperandrogenism and oligo-ovulation, and it is often associated with poor reproductive performance. Using immunohistochemistry and reverse transcription-polymerase chain reaction, we found that women with PCOS exhibited elevated endometrial AR expression compared to normal, fertile controls. This increase was most apparent in glandular and luminal epithelium. Furthermore, when compared to endometrium from fertile women, PCOS endometrium showed other abnormalities in endometrial development, including delay or absence of the alpha(v)beta3 integrin, a well-characterized biomarker of uterine receptivity described previously (Lessey et al., JCI 1992; 90:188-195). To better understand and to gain insights regarding these findings, we used in vitro cell-culture models to study the regulation of AR in primary endometrial stromal and the well-differentiated epithelial cell line (Ishikawa). Based on Western blot analysis, epithelial AR is up-regulated by estrogens and androgens and is inhibited by progestins and epidermal growth factor (EGF). On the other hand, EGF significantly induced the expression of alpha(v)beta3, whereas estrogen and androgen treatment inhibited its expression. Collectively, these results suggest that the poor reproductive performance observed in women with PCOS may be due, in part, to the concomitant increase in both serum androgens and elevations in endometrial AR. This combination may reduce endometrial receptivity as judged by the down-regulation of alpha(v)beta3 integrin.