title: Intracrine Androgens Enhance Decidualization and Modulate Expression of Human Endometrial Receptivity Genes.
abstract: The endometrium is a complex, steroid-dependent tissue that undergoes dynamic cyclical remodelling. Transformation of stromal fibroblasts (ESC) into specialised secretory cells (decidualization) is fundamental to the establishment of a receptive endometrial microenvironment which can support and maintain pregnancy. Androgen receptors (AR) are present in ESC; in other tissues local metabolism of ovarian and adrenal-derived androgens regulate AR-dependent gene expression. We hypothesised that altered expression/activity of androgen biosynthetic enzymes would regulate tissue availability of bioactive androgens and the process of decidualization. Primary human ESC were treated in vitro for 1-8 days with progesterone and cAMP (decidualized) in the presence or absence of the AR antagonist flutamide. Time and treatment-dependent changes in genes essential for a) intra-tissue biosynthesis of androgens (5α-reductase/SRD5A1, aldo-keto reductase family 1 member C3/AKR1C3), b) establishment of endometrial decidualization (IGFBP1, prolactin) and c) endometrial receptivity (SPP1, MAOA, EDNRB) were measured. Decidualization of ESC resulted in significant time-dependent changes in expression of AKR1C3 and SRD5A1 and secretion of T/DHT. Addition of flutamide significantly reduced secretion of IGFBP1 and prolactin and altered the expression of endometrial receptivity markers. Intracrine biosynthesis of endometrial androgens during decidualization may play a key role in endometrial receptivity and offer a novel target for fertility treatment.
authors.affiliation: Medical Research Council Centre for Inflammation Research, The University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ. UK.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Gibson
authors.affiliation: Medical Research Council Centre for Inflammation Research, The University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ. UK.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Simitsidellis
authors.affiliation: Medical Research Council Centre for Inflammation Research, The University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ. UK.
authors.forename: Fiona L
authors.initials: FL
authors.lastname: Cousins
authors.affiliation: Medical Research Council Centre for Reproductive Health, The University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ. UK.
authors.forename: Hilary O D
authors.initials: HO
authors.lastname: Critchley
authors.affiliation: Medical Research Council Centre for Inflammation Research, The University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ. UK.
authors.forename: Philippa T K
authors.initials: PT
authors.lastname: Saunders
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics; D000728:Androgens / Q000378:metabolism*; D003656:Decidua / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D011247:Pregnancy; D013739:Testosterone / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D000728:Androgens; D008565:Membrane Proteins; D013739:Testosterone; D005485:Flutamide; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548467:SRD5A1 protein, human
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