Telephone: 0131-242-6388 [direct],
PA: Madeleine Stevenson [0131-242-6240]
Sex steroids including oestrogens and androgens are ‘master regulators’ of the reproductive system and also have an impact on our bones, brain as well as blood vessels and our immune system. Oestrogens and androgens are synthesised by cells within the ovaries and testes as well as those in other tissues e.g. adipose and skin. Local concentrations of steroids are also modulated within target tissues, a feature of human tissues known as ‘intracrinology’ as a result of presence of enzymes such as aromatase (converts testosterone to oestradiol). Steroids classically regulate tissue function by binding to receptors that function as ligand activated transcription factors. There are two oestrogen receptors usually called ERalpha and ERbeta, and a single androgen receptor. The impact of oestrogens and androgens on the function of the different cells types within reproductive tissues is determined by the ‘cocktail’ of available receptors as well as availability of co-factors.
Our studies are directed at understanding the mechanisms responsible for the impact of steroids in normal reproductive tissues and also in disorders associated with reproductive tissue malfunction. A primary interest of the current research effort is directed at determining how oestrogens and androgens regulate the function of the endometrium (the lining of the womb). We now appreciate that the endometrium itself my also metabolise steroids ensuring a locally high concentration [PDF]. During a women’s reproductive life the endometrium retains a remarkable degree of developmental plasticity that allows it to adapt to the challenges imposed by the menstrual cycle and pregnancy. Our recent studies [PDF] have provided novel insights into the cellular processes that contribute to the rapid scarless healing and re-epithelialisation that occurs at the time of menses limiting blood loss implicating both epithelial cell migration and mesenchymal cell differentiation (MET) in restoration of an intact epithelial cell layer. We use a wide variety of molecular and cellular models including primary human cells growing on 3D matrices together with genomic analysis, bioinformatics and cell imaging.
We are working closely with clinical colleagues based in the Centre and experts in translational research funding based in the Bioquarter to ensure our results result in new, non-surgical therapies for women suffering from heavy periods (coll Hilary Critchley), from chronic pelvic pain and endometriosis (coll Andrew Horne) and endometrial and other cancers.
For a brief video describing the work please click here »
- Congratulations to Ioannis – the image of the mouse uterus shown on this page has been selected as the cover image for the Journal of Endocrinology.
- Congratulations to Fiona and Erin for being selected to give talks at prestigious International meetings in Florence and San Paulo in March and May 2014.
- Doug has been successful in obtaining a grant from the Cancer Centre for his innovative studies on obesity and endometrial cancer following on from ideas developed in his recent reviews in Endocrine Related Cancer.
Current research projects
• The role of androgens in women’s health – fertility and endometriosis.
• Impact of sex steroids on immune and vascular cell function in the reproductive system.
• Steroids and reproductive regeneration and resilience.
- MRC Centre for Reproductive Health 2011-2016. Lead Applicant. £1,086,025 [G1002033]
- MRC Programme Grant 2011-2016. Impact of sex steroids on immune and vascular cell function in the reproductive system. £3.8 million
- MRC Next Generation Optical Imaging initiative: Integrated multi-dimensional molecular organ imaging. 2013-2016. £1.6 million Co-I [PI Pollard].
- QMRI Mass Spectometry Facility. Co-Applicants Andrew, Walker, Newby, Webster, Saunders. 2010-2015. £739, 245.
- QMRI FACS facility core funding. Wellcome Trust. Coapplicants: Anderton, Haslett, Saunders, Gregory, ffrench-Constant. 2009-2014. £550,000
- 2008- Tommy’s the Baby Charity Research Charity, University of Edinburgh Pregnancy Research Centre Co-applicants: Calder, Hughes, Saunders, Seckl, Walker, Newby, Reynolds, Denison. ~£400k pa.
Selected Recent Publications [H index = 55]
Gibson DA, Simitsidellis I, Collins F, Saunders PTK. (2014) Evidence of androgen action in endometrial and ovarian cancers. Endocrine Related Cancer. [http://dx.doi.org/10.1530/ERC-13-0551]
Cousins FL, Murray A, Esnal A, Gibson DA, Critchley HOD, Saunders PTK. (2014) Evidence from a mouse model that epithelial cell migration and mesenchymal-epithelial transition contribute to rapid restoration of uterine tissue integrity during menstruation. PLoSONE 9(1): e86378. doi:10.1371/journal.pone.0086378.
Gibson DA, Saunders PTK. (2013) Disruption of estrogen signalling by endocrine disruptors in female reproductive tract cancers. Endocrine Related Cancer. Oct 25. [Epub ahead of print] PMID: 24163391.
Gibson DA, McInnes KJ, Critchley HOD, Saunders PTK. (2013) Endometrial intracrinology – generation of an estrogen-dominated microenvironment in the secretory phase of women. 98:E1802-6.
Greaves E, Collins F, Critchley HOD, Saunders PTK. (2013) ERβ-dependent effects on uterine endothelial cells are cell-specific and mediated via Sp1. Human Reproduction. 28, 2490-2501.
Young VJ, Brown JK, Saunders PTK, Horne, AW. (2013) The Role of the Peritoneum in the Pathogenesis of Endometriosis. Human Reproduction Update. 19, 558-569.
McInnes KJ, Smith LB, Hunger NI, Saunders PTK, Andrew R, Walker BR. (2012) Deletion of the androgen receptor in adipose tissue in male mice elevates retinol binding protein 4 and reveals independent effects on visceral fat mass and on glucose homeostasis. Diabetes. 61:1072–1081.
Marshall E, Lowrey J, Sheila Macpherson S, Maybin JA, Collins F, Critchley HOD, Saunders PTK. (2011) In silico analysis identifies a novel role for androgens in the regulation of human endometrial apoptosis. J Clin Endo Metab 96 (11): E1746-55.
Dr Erin Greaves (Postdoc MRC funded)
Dr Douglas Gibson (Postdoc MRC funded)
Fiona Cousins Postdoc 2013-2014. MRC Funded
Frances Collins (Lab manager, MRC funded)
Arantza Esnal (Senior Research Support, MRC Funded)
James Martin (Research Support, MRC Funded)
Ioannis Simitsidellis (PhD student 2012-2015) Principals Career Development Fellowship CMVM
Bianca DeLeo (PhD student 2013-2016) MRC Centre Grant
Sharon Macpherson (Research Nurse, MRC funded)
Madeleine Stevenson PA (p/t, M, W,Th)
Hilary Critchley, Andrew Horne, Richard Sharpe, Lee Smith, Jane Norman (CRH)
Sarah Howie, Adriano Rossi (MRC-CIR), Stuart Forbes (MRC-CIR)
Tom Freeman (Roslin), Sue Fleetwood-Walker (SBMS)
Prof Thomas D’Hooghe (Leuven, Belgium), Sylvia Meschner (Berlin).
2010- Fellow Society of Biology (FSB)
2012 – Fellow Academy of Medical Sciences (FMedSci)
Current Positions of Responsibility
Director of Postgraduate Research (PGR), College of Medicine and Veterinary Medicine 2012-
Member MRC Population and Systems Medicine Board (PSMB) 2012-
Academy of Medical Sciences, Academic Careers Committee. 2013-
Society for Endocrinology: Science Committee 2012- , Faculty Lead Early Career Researcher Training 2013, Finance Committee 2014-
Scientific Advisory Board, UoE Tommy’s Centre for Fetal and Maternal Health 2008-
Ethical Review Panel University of Edinburgh Biological Services 2003-
1979- Society for the Study of Fertility (Committee member 1990-1993)
1987- British Society for Endocrinology
1990- British Society for Cell Biology
1993- Society of the Study of Reproduction (USA)
1997- Endocrine Society USA
2009- Society for Gynecological Investigation