The Role of the Glucocorticoid Receptor Signalling Pathway within the Human Endometrium

Samantha Thomas, Thomas SJ
In: Swansea University · 2019 · doi:10.23889/suthesis.50584 · W2982045529
dissertation OA: closed CC0
Full text JSON View on OpenAlex View at publisher
⚙ AI-generated summary by claude@2026-06+body, 2026-06-11 ⓘ

This study investigated the expression and role of the glucocorticoid receptor (GR) signaling pathway in the human endometrium, finding altered GR and cortisol levels in infertile patients and a detrimental effect of stress hormone activation on decidualization.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 · read from full text ⓘ

This Ph.D. thesis investigated glucocorticoid receptor (GR) signaling in the human endometrium, using endometrial samples from fertile and infertile patients and combining immunohistochemistry with cell culture, qPCR, immunoblotting, ELISAs, and chromatin immunoprecipitation to assess GR activity during decidual transformation. The study found that circulating cortisol levels and endometrial GR expression vary across the menstrual cycle with lowest values in the secretory phase, while infertile patients showed significantly higher cortisol and GR levels. In vitro GR activation was crucial for reproductive processes in fertile patients but, in the presence of cortisol, delayed decidualization and further worsened an already hindered decidual response in infertile patients; these cortisol effects were inhibited by a GR antagonist, and ChIP supported GR binding to target gene promoters during decidualization. The thesis concludes that stress-axis activation via GR is detrimental to key reproductive functions and that GR/MR dominance and GR–sex steroid crosstalk are altered in infertility, relating these findings to reproductive endocrinological pathologies including endometriosis; relevance to endometriosis is explicitly addressed as part of the infertile patient conditions linked to altered GR/cortisol patterns, though the thesis focuses broadly on GR signaling in the endometrium rather than exclusively on endometriosis.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

The activation of the stress-responsive biological system, known as the hypothalamic-pituitary-adrenal axis leads to an increase in the synthesis of the glucocorticoids (GCs). The GCs regulate a number of diverse biological processes within the body by altering the transcription of an array of steroid responsive genes, mediated by the glucocorticoid receptor (GR). Along with the well-characterised sex steroid hormones, the human endometrium is also targeted by GCs due to the presence of GR within the healthy human endometrium Nevertheless, research is lacking in elucidating the role of stress and hence the GR signalling pathway on reproductive functions and fertility. Objectives: The principal aims were to present novel evidence for the expression of GCs and its nuclear receptor; GR in the endometrium of fertile and infertile patients and to relate these observations to key features of common reproductive endocrinological pathologies namely PCOS, endometriosis and unexplained infertility (UI). Secondary to this, was to establish the effect of GR signalling pathway activation in the process of endometrial decidual transformation in fertile and infertile patients. Methodology: This project employed the use of ... (continues)
Full text 4,216 characters · extracted from oa-doi-fallback · click to expand
E-Thesis 1016 views 199 downloads The Role of the Glucocorticoid Receptor Signalling Pathway within the Human Endometrium / Samantha Thomas - PDF | Redacted version - open access Download (14.52MB) DOI (Published version): 10.23889/Suthesis.50584 Abstract Summary:The activation of the stress-responsive biological system, known as the hypothalamic-pituitary-adrenal axis leads to an increase in the synthesis of the glucocorticoids (GCs). The GCs regulate a number of diverse biological processes within the body by altering the transcription of an array... | Published: | Swansea 2019 | |---|---| | Institution: | Swansea University | | Degree level: | Doctoral | | Degree name: | Ph.D | | URI: | https://cronfa.swan.ac.uk/Record/cronfa50584 | | Abstract: | Summary:The activation of the stress-responsive biological system, known as the hypothalamic-pituitary-adrenal axis leads to an increase in the synthesis of the glucocorticoids (GCs). The GCs regulate a number of diverse biological processes within the body by altering the transcription of an array of steroid responsive genes, mediated by the glucocorticoid receptor (GR). Along with the well-characterised sex steroid hormones, the human endometrium is also targeted by GCs due to the presence of GR within the healthy human endometrium Nevertheless, research is lacking in elucidating the role of stress and hence the GR signalling pathway on reproductive functions and fertility.Objectives:The principal aims were to present novel evidence for the expression of GCs and its nuclear receptor; GR in the endometrium of fertile and infertile patients and to relate these observations to key features of common reproductive endocrinological pathologies namely PCOS, endometriosis and unexplained infertility (UI). Secondary to this, was to establish the effect of GR signalling pathway activation in the process of endometrial decidual transformation in fertile and infertile patients.Methodology:This project employed the use of immunohistochemistry (IHC), cell culture, Real-time polymerase chain reaction (qPCR), immunoblotting, enzyme linked immunosorbant assays (ELISAs), chromatin immunoprecipitation (ChIP), cell morphology analysis and TRANSFAC promoter analysis.Results:Circulating cortisol levels and endometrial GR expression follow a distinct expression pattern throughout the normal menstrual cycle, with the lowest levels being observed during the secretory phase. Conversely, infertile patients exhibited significantly higher levels of both. In vitro analysis revealed that activation of the GR signalling pathway, although crucial for reproductive processes in the fertile patients, can result in delayed decidualization in the presence of the stress hormone cortisol. The effect of stress on the decidual response was able to be inhibited when a GR antagonist was used. ChIP analysis confirmed the presence of GR on the promoter regions of target genes in the presence of GCs during decidual transformation. An already hindered decidual response present in infertile patients was further exacerbated in the presence of the stress hormone. Moreover, a genetic switch from GR to mineralocorticoid receptor (MR) dominance, crucial for successful decidualization is inhibited in the infertile patients. Finally, a degree of crosstalk between GR and the sex steroid hormone signalling pathways also takes place during endometrial decidual transformation.Conclusion:In conclusion, it is apparent that the GR signalling pathway plays a crucial role in reproduction in the absence of the stress response. However, endometrial GR expression and circulating levels of the stress hormone cortisol is altered in infertile patients diagnosed with PCOS, endometriosis and UI. The activation of the GR signalling pathway due to the presence of the stress hormone cortisol is detrimental for crucial reproductive functions, including decidualization in both fertile and infertile patients. | |---|---| | Item Description: | A selection of third party content is redacted or is partially redacted from this thesis. | | Keywords: | Glucocorticoid receptor, decidualization, stress, infertility | | College: | Faculty of Medicine, Health and Life Sciences |

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

⚙ Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback ⓘ

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (100)

Source provenance

europepmc
last seen: 2026-08-12T06:07:16.479679+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
unpaywall
last seen: 2026-06-02T02:00:03.124865+00:00
License: CC0 · commercial use OK