Cited by 76Estrogen and related hormone effectsEndometrial and Cervical Cancer TreatmentsReproductive System and Pregnancy

Androgens, oestrogens and endometrium: a fine balance between perfection and pathology

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Gibson, Douglas A, Simitsidellis, Ioannis, Collins, Frances, Saunders, Philippa T K·2020·Journal of Endocrinology

Abstract

The endometrium is a complex multicellular tissue that is exquisitely sensitive to the actions of sex steroids synthesised in the ovary (endocrine system). Recent studies have highlighted a previously under-appreciated role for local (intracrine) metabolism in fine-tuning tissue function in both health and disease. In this review we have focused on the impact of oestrogens and androgens on endometrial function summarising data from studies on normal endometrial physiology and disorders including infertility, endometriosis and cancer. We consider the evidence that expression of enzymes including aromatase, sulphatase and AKR1C3 by endometrial cells plays an important role in tissue function and malfunction and discuss results from studies using drugs targeting intracrine pathways to treat endometrial disorders. We summarise studies exploring the spatial and temporal expression of oestrogen receptors (ERalpha/ESR1, ERbeta/ESR2 and GPER) and their role in mediating the impact of endogenous and synthetic ligands on cross-talk between vascular, immune, epithelial and stromal cells. There is a single androgen receptor gene and androgens play a key role in stromal-epithelial cross-talk, scar-free healing of endometrium during menstruation and regulation of cell proliferation. The development of new receptor-selective drugs (SERMs, SARMs, SARDs) has reinvigorated interest in targeting receptor subtypes in treatment of disorders including endometriosis and endometrial cancer and some show promise as novel therapies. In summary, understanding the mechanisms regulated by sex steroids provides the platform for improved personalised treatment of endometrial disorders as well as novel insights into the impact of steroids on processes such as tissue repair and regeneration.

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Crossref · 10.1530/joe-20-0106

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  • Potential sources of altered androgen metabolism in endometriosis could be the lesions themselves, as endometrial cells have been shown to have the capacity to express the full complement of the steroidogenic genes involved in androgen and estrogen synthesis.

    “Potential sources of altered androgen metabolism in endometriosis could be the lesions themselves, as endometrial cells have been shown to have the capacity to express the full complement of the steroidogenic genes involved in androgen and estrogen synthesis.28”

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Research works printed but not linked: 3

  1. Sanderson PA, Critchley HO, Williams AR, Arends MJ & Saunders PT 2017 New concepts for an old problem: the diagnosis of endometrial hyperplasia. Hum Reprod Update 23 232-254.
  2. Saunders PT, Millar MR, Macpherson S, Irvine DS, Groome NP, Evans LR, Sharpe RM & Scobie GA 2002 ERbeta1 and the ERbeta2 splice variant (ERbetacx/beta2) are expressed in distinct cell populations in the adult human testis. J Clin Endocrinol Metab 87 2706-2715.
  3. Shaaban AM, Green AR, Karthik S, Alizadeh Y, Hughes TA, Harkins L, Ellis IO, Robertson JF, Paish EC, Saunders PT, et al. 2008 Nuclear and cytoplasmic expression of ERbeta1, ERbeta2, and ERbeta5 identifies distinct prognostic outcome for breast cancer patients. Clin Cancer Res 14 5228- 5235.

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Authors
Gibson, D. A., Simitsidellis, I., Collins, F., & Saunders, P. T. K.
Affiliations
Centre for Inflammation Research (GB)
Corresponding author
Saunders, Philippa T K
Venue
Journal of Endocrinology
Published
2020-09
Volume
246
Issue
3
Pages
R75-R93
ISSN
  • 0022-0795 (ISSN-L)
  • 1479-6805
OpenAlex
W3034379618
Cited by
76
References
181
Citations by year
2026: 9 · 2025: 11 · 2024: 17 · 2023: 15 · 2022: 15 · 2021: 8 · 2020: 1
FWCI
1.40
Type
journal article
Language
en
Open access
Locations
  • Journal of Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
Funders
Medical Research Council (MR/N024524/1, G1100356/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Keywords
endometrium, sex steroids, estrogen, androgens, aromatase, sulphatase, AKR1C3, oestrogen receptor, androgen receptor, endometriosis, endometrial cancer, infertility, tissue repair, selective estrogen receptor modulators, selective androgen receptor modulators, tissue regeneration
MeSH terms
Androgens, Endometriosis, Endometrium, Estrogens, Female, Humans, Estrogen Receptor alpha

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