Fallopian tube epithelial cells express androgen receptor and have a distinct hormonal responsiveness when compared with endometrial epithelium

Abstract

STUDY QUESTION: How does steroid receptor expression, proliferative activity and hormone responsiveness of the fallopian tube (FT) epithelium compare to that of the endometrial epithelium? SUMMARY ANSWER: Proliferative indices, hormone receptor expression-scores and in vitro response to oestrogen and androgens of the human FT demonstrate a distinct pattern from the matched endometrium. WHAT IS KNOWN ALREADY: The FT epithelium exists as a continuum of the endometrium, and both express steroid hormone receptors. The ovarian steroid hormones regulate cyclical proliferation and regeneration of the endometrium, but their effects on steroid hormone receptor expression and proliferation in the FT have not yet been fully elucidated. STUDY DESIGN, SIZE, DURATION: We included women with proven fertility, undergoing hysterectomy and bilateral salpingooophorectomy for benign, gynaecological conditions at Liverpool Women's NHS Foundation Trust. They had no known endometrial or tubal pathology and were not on hormonal treatments for at least 3 months preceding sample collection in this prospective observational study (conducted between 2010 and 2018). A full-thickness sample of the endometrium and a sample from the FT were collected from each woman. PARTICIPANTS/MATERIALS, SETTING, METHODS: The differential protein and mRNA levels of steroid hormone receptors, oestrogen receptors a and b, androgen receptor (AR) and progesterone receptor (PR), and the proliferative marker (Ki67) of the endometrium and the FT tissue samples from 47 healthy women undergoing surgery (37 premenopausal and 10 postmenopausal) were investigated using immunohistochemistry and quantitative real-time PCR. The comparative responsiveness to oestrogen and androgen of the endometrium and the fimbrial end of the FT was analysed using an in vitro short-term explant culture model. The endpoints assessed in the explants were the changes in mRNA and protein levels for AR, PR and the epithelial proliferative index after 24 h treatment with oestradiol (E2) or dihydrotestosterone (DHT). MAIN RESULTS AND THE ROLE OF CHANCE: The premenopausal endometrial functionalis glands (FG) displayed the well-known cyclic variation in cellular proliferation and steroid receptor scores. Compared with the endometrial FG, the matched FT epithelium (both fimbrial or isthmic ends) displayed a significantly lower proportion of cells expressing Ki67 (2.8% § 2.2%, n ¼ 18 vs 30.0% § 26.3%, n ¼ 16, P ¼ 0.0018, respectively) accompanied with a significantly higher AR immunoscores (6.7 § 2.7, n ¼ 16 vs 0.3 § 1.0, n ¼ 10, P ¼ 0.0136). The proportion of cells expressing Ki67 and the AR immunoscores of the FT epithelium correlated positively with endometrial luminal epithelium (r ¼ 0.62, P ¼ 0.005, and r ¼ 0.68, P ¼ 0.003, respectively). In vitro experiments suggested the tubal explants to be apparently less responsive to E2 yet more sensitive to DHT compared with the matched endometrium explants.