title: Characterization of androgen receptors in a well-differentiated endometrial adenocarcinoma cell line (Ishikawa).
abstract: Androgen receptors (AR) have been identified in the human endometrium, but their role in endometrial function and development towards endometrial receptivity remains poorly understood. In an effort to study the regulation and possible function in endometrial epithelium, we utilized the well-differentiated endometrial adenocarcinoma cell line, Ishikawa, as a model system. This cell line has proven to be stable, hormonally responsive, contains both estrogen and progesterone receptors, and has been shown to express endometrial proteins in a hormone responsive manner. In the present study, we demonstrate that Ishikawa cells also express AR, based on immunohistochemical staining, radioactive binding studies, RT-PCR and Northern blot analysis. The expression of AR is induced in Ishikawa cells by estrogens, similar to that reported for normal endometrium. Further, using an estrogen-responsive gene that has been characterized in this cell line, alkaline phosphatase, we show that androgens act as antiestrogens in diethylstilbestrol (DES) treated cells, inhibiting enzymatic activity in a dose-dependent manner. These data support a physiologic role for AR in the endometrium. Elevations in endometrial AR in certain clinical situations such as polycystic ovarian syndrome (PCOS) may amplify the effects of androgens on the endometrium leading to suspected defects in uterine receptivity, higher than expected infertility and high miscarriage rates observed in patients with this disorder.
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, CB # 7570 Old Clinic Building, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7570, USA.
authors.forename: L P
authors.initials: LP
authors.lastname: Lovely
authors.forename: K B
authors.initials: KB
authors.lastname: Appa Rao
authors.forename: Y
authors.initials: Y
authors.lastname: Gui
authors.forename: B A
authors.initials: BA
authors.lastname: Lessey
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D000728:Androgens / Q000378:metabolism / Q000494:pharmacology; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D004054:Diethylstilbestrol / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D016889:Endometrial Neoplasms / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005485:Flutamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077267:Fulvestrant; D006801:Humans; D015741:Metribolone / Q000378:metabolism / Q000494:pharmacology; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology; D011944:Receptors, Androgen / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000728:Androgens; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D000077267:Fulvestrant; D015741:Metribolone; C014290:hydroxyflutamide; D011374:Progesterone; D004958:Estradiol; D004054:Diethylstilbestrol; D005485:Flutamide; D000469:Alkaline Phosphatase