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PMID: 26817618 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Intracrine Androgens Enhance Decidualization and Modulate Expression of Human Endometrial Receptivity Genes.

Scientific reports ·Vol. 6 ·2016-01-28 ·Pages 19970

Gibson DA, Simitsidellis I, Cousins FL, Critchley HO, Saunders PT

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.

MeSH Terms
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics Androgens/metabolism Decidua/metabolism Endometrium/metabolism Female Flutamide/pharmacology Gene Expression Regulation/drug effects Humans Membrane Proteins/genetics Pregnancy Testosterone/biosynthesis,metabolism
Chemicals
Androgens Membrane Proteins Testosterone Flutamide 3-Oxo-5-alpha-Steroid 4-Dehydrogenase SRD5A1 protein, human
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Gibson Douglas A
Medical Research Council Centre for Inflammation Research, The University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ. UK.
Simitsidellis Ioannis
Medical Research Council Centre for Inflammation Research, The University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ. UK.
Cousins Fiona L
Medical Research Council Centre for Inflammation Research, The University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ. UK.
Critchley Hilary O D
Medical Research Council Centre for Reproductive Health, The University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ. UK.
Saunders Philippa T K
Medical Research Council Centre for Inflammation Research, The University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ. UK.
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Article Info
Journal
Scientific reports
Abbr.
Sci Rep
ISSN
2045-2322
DOI
10.1038/srep19970
Published
2016-01-28
Epub
2016-00-28
Pages
19970
Language
English
Region
England
NLM ID
101563288
PMCID
PMC4730211
Subset
IM
Grants
Medical Research Council · MR/N022556/1 · United Kingdom
Medical Research Council · MR/N024524/1 · United Kingdom
Medical Research Council · G1100356/1 · United Kingdom
External Links
PubMed source DOI: 10.1038/srep19970 PMC Full Text View journal details
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