A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus

Ioannis Simitsidellis, Douglas A Gibson, Fiona L Cousins, Arantza Esnal-Zufiaurre, Philippa Tk Saunders

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The endometrium consists of stromal and epithelial compartments (luminal and glandular) with distinct functions in the regulation of uterine homeostasis. Ovarian sex steroids, namely 17β-estradiol (E2) and progesterone (P4), play essential roles in modulating uterine cell proliferation, stromal-epithelial cross-talk and differentiation in preparation for pregnancy. The impact of androgens on uterine function remains poorly understood. The current study investigated the impact of the non-aromatizable androgen dihydrotestosterone (DHT) on mouse endometrial function. Ovariectomized female mice were given a single subcutaneous injection (short treatment) or 7 daily injections (long treatment) of vehicle alone (5% ethanol, 0.4% methylcellulose) or vehicle with the addition of 0.2 mg DHT (n=8/group) and a single injection of Bromodeoxyuridine (BrdU) 2 hours prior to tissue recovery. Treatment with DHT increased uterine weight, the area of the endometrial compartment and immunoexpression of the androgen receptor (AR) in the luminal and glandular epithelium. Treatment-dependent proliferation of epithelial cells was identified by immunostaining for MKi67 and BrdU. Quantitative RT-PCR identified significant DHT-dependent changes in the concentrations of mRNAs encoded by genes implicated in the regulation of the cell cycle (Wee1, Ccnd1, Rb1) and stromal-epithelial interactions (Wnt4, Wnt5a, Wnt7a, Cdh1, Vcl, Igf1, Prl8, Prlr) as well as a striking impact on the number of endometrial glands. This study has revealed a novel role for androgens in regulating uterine function with an impact on the glandular compartment of the endometrium. This previously unrecognised role for androgens has implications for our understanding of the role of androgens in regulation of endometrial function and fertility in women.

Original languageEnglish
Pages (from-to)en20152032
JournalEndocrinology
Early online date10 Mar 2016
DOIs
Publication statusE-pub ahead of print - 10 Mar 2016

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