Endocrine Abstracts (2019) 65 PL9 | DOI: 10.1530/endoabs.65.PL9

Sex steroids and the endometrium: dynamics and disorders

Douglas Gibson, Frances Collins, Ioannis Simisidellis, Phoebe Kirkwood, Arantza Esnal-Zufiaurre & Philippa Saunders

The University of Edinburgh, Edinburgh, UK

The endometrium is a complex tissue with luminal and glandular epithelial cell layers supported on a multicellular stromal compartment; in women the inner (luminal) portion of the tissue breaks down and is shed during menstruation. The endometrium is exquisitely sensitive to the actions of sex steroids (oestrogens, progestogens and androgens) produced in ovarian and other extra gonadal tissues and delivered via blood vessels that rapidly develop and mature within the tissue (endocrine system). Our own studies have recently highlighted a previously under-appreciated role for local (intracrine) pathways in fine-tuning tissue function to support implantation. We have used cell, tissue and animal models to explore the role of oestrogen and androgen receptors, and their natural ligands, in normal endometrial function and to determine how these are dysregulated in disorders including infertility, endometriosis and cancer. We have documented dynamic, spatial and temporal expression of both full-length (wild type) oestrogen receptors and ER splice variant isoforms during the normal cycle and identified changes in response to malignant transformation. We have shown oestrogens play a key role in regulating the function of immune cells that play an important role in preparation for implantation and in the formation and survival of extra-uterine endometriosis lesions. Studies using DHT and selective androgen receptor modulators (SARMs) have confirmed a role for androgen receptor mediated pathways in regulating stromal-epithelial cross talk. In summary, understanding the mechanisms regulated by sex steroid receptors in the endometrium provides the platform for improved medical therapies for endometrial disorders as well as novel insights into the impact of steroids on processes such as angiogenesis and tissue repair.

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