Characterization of androgen receptors in a well-differentiated endometrial adenocarcinoma cell line (Ishikawa)

Androgen receptors (AR) have been identified in the human endometrium, but their role in endometrial Function and development towards endometrial rece ptivity remains poorly understood. In an effort to study the regulation and possible function in endometrial epithelium, we utilized the well-differen tiated endometrial adenocarcinoma cell line, Ishikawa, as a model system. T his cell line has proven to be stable, hormonally responsive, contains both estrogen and progesterone receptors, and has been shown to express endomet rial proteins in a hormone responsive manner. In the present study, we demo nstrate that Ishikawa cells also express AR, based on immunohistochemical s taining, radioactive binding studies, RT-PCR and Northern blot analysis. Th e expression of AR is induced in Ishikawa cells by estrogens, similar to th at reported for normal endometrium. Further, using an estrogen-responsive g ene that has been characterized in this cell line, arkaline phosphatase, we show that androgens act as antiestrogens in diethylstilbestrol (DES) treat ed cells, inhibiting enzymatic activity in a dose-dependent manner. These d ata support a physiologic role for AR in the endometrium. Elevations in end ometrial AR in certain clinical situations such as polycystic ovarian syndr ome (PCOS) may amplify the effects of androgens on the endometrium leading to suspected defects in uterine receptivity, higher than expected infertili ty and high miscarriage rates observed in patients with this disorder. (C) 2000 Elsevier Science Ltd. All rights reserved.