Endocrine Abstracts

In women, establishment of pregnancy is dependent upon ‘fine-tuning’ of the endometrial microenvironment which is mediated by differentiation (decidualisation) of human endometrial stromal fibroblasts (hESF). Using a robust in vitro model of decidualisation we have demonstrated an important role for local steroid metabolism in regulating hESF, something previously considered a solely endocrine-mediated process. We have conducted detailed time-course profiling of the steroidogenic capacity of hESF during decidualisation and established that expression of aromatase, the key enzyme required for synthesis of estrogens, as well as enzymes that convert precursor androgens into active testosterone and dihydrotestosterone (AKR1C3; SRD5A1) are altered in a time-dependent manner. Expression of these enzymes results in increased biosynthesis of potent steroid receptor agonists (estrogens and androgens) that in turn regulate expression of genes important for endometrial receptivity and immune cell-mediated vascular remodelling. Our recent studies demonstrate that bioavailability of circulating precursors including dehydroepiandrosterone, as well as sulfated steroids, also contribute to local tissue steroid concentrations and impact on decidualisation. Collectively, these findings represent a paradigm shift in our understanding of the importance of local sex steroid action in the endometrium during the establishment of pregnancy, highlighting new therapeutic targets for reproductive health and disease.