Cyclooxygenase enzymes and prostaglandins in pathology of the endometrium
Open accessAbstract
Prostaglandins are bioactive lipids produced from arachidonic acid by cyclooxygenase (COX) enzymes and specific terminal prostanoid synthase enzymes. After biosynthesis, prostaglandins exert an autocrine-paracrine function by coupling to specific prostanoid G protein-coupled receptors to activate intracellular signalling and gene transcription. For many years, prostaglandins have been recognized as key molecules in reproductive biology by regulating ovulation, endometrial physiology and proliferation of endometrial glands and menstruation. More recently, a role for COX enzymes and prostaglandins has been ascertained in reproductive tract pathology, including carcinomas, menorrhagia, dysmenorrhoea and endometriosis. Although the mechanism by which prostaglandins modulate these pathologies is still unclear, a large body of evidence supports a role for COX enzymes, prostaglandins and prostaglandin receptor signalling pathways in angiogenesis, apoptosis and proliferation, tissue invasion and metastases and immunosuppression. Here, an overview is provided of some of the findings from these studies with specific emphasis on the role of COX enzymes, prostaglandin E(2) and F2α in disorders of endometrial proliferation and menstruation in non-pregnant women.
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In cancers of the breast, endometrium and ovary, CYP19A1 expression is primarily regulated by increased activity of the I.3/II promoter region, which can be upregulated by prostaglandins such as PGE2.
“Notably, Bulun and colleagues have found that in cancers of breast, endometrium and ovary, expression is primarily regulated by increased activity of the I.3/II promoter region, which can be upregulated by prostaglandins such as PGE2, providing a link between the overexpression of PGs that has been reported to occur in EC [79] and intracrine oestrogen biosynthesis [80].”
From Endometrial Intracrinology: Oestrogens, Androgens and Endometrial Disorders (2018) · cites this paper as [79]
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Cites
Sampson, J. A. (1927) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(15)30003-x · Cited by 2,334 · see citing works
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Expression of estrogen receptor alpha and beta in peritoneal and ovarian endometriosis
Matsuzaki, S., Murakami, T., Uehara, S., Canis, M., Sasano, H., & Okamura, K. (2001) · Fertility and Sterility · doi:10.1016/s0015-0282(01)01783-6 · Cited by 133 · cited 1× · see citing works
“Endometriosis is an oestrogen-dependent disorder and immunohistochemical studies have localized oestrogen receptor expression and increased expression of aromatase in epithelial and stromal cells of endometriotic tissues and peritoneum (Matsuzaki et al., 2001; Bulun et al., 2002b).”
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Endometrial Intracrinology: Oestrogens, Androgens and Endometrial Disorders
Gibson, D. A., Simitsidellis, I., Collins, F., & Saunders, P. T. K. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103276 · Cited by 70 · see citing works
“3/II promoter region, which can be upregulated by prostaglandins such as PGE2, providing a link between the overexpression of PGs that has been reported to occur in EC [79] and intracrine oestrogen biosynthesis [80].”
BackgroundNaem, A., Krentel, H., Moawad, G., Naem, J., Venezia, R., Etrusco, A., Terzic, S., & Laganà, A. S. (2024) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2024.102500 · Cited by 15 · see citing works
Lousse, J.-C., Defrère, S., Ramos, R. G., Van Langendonckt, A., Colette, S., & Donnez, J. (2009) · Journal of Endometriosis · doi:10.1177/228402650900100104 · Cited by 10 · see citing works
- Authors
- Sales, K. J., & Jabbour, H. N.
- Affiliations
- MRC Centre for Reproductive Health (GB)
- ORCID
- Sales, K J
- Venue
- Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-11-01
- Volume
- 126
- Issue
- 5
- Pages
- 559-567
- ISSN
- 1470-1626 (ISSN-L)
- 1741-7899
- PMC
- PMC2695735
- OpenAlex
- W2155438634
- Cited by
- 177
- References
- 3
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 10 · 2023: 4 · 2022: 5 · 2021: 9 · 2020: 9 · 2019: 5 · 2018: 7 · 2017: 8 · 2016: 8 · 2015: 5 · 2014: 11 · 2013: 6 · 2012: 13
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Reproduction (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Menstrual Health and Disorders
- Keywords
- cyclooxygenase, prostaglandins, endometrium, endometrial pathology, prostaglandin E2, prostaglandin F2alpha, endometriosis, menorrhagia, dysmenorrhea, endometrial cancer, menstruation, endometrial proliferation, angiogenesis, apoptosis, metastasis, immunosuppression, prostanoid receptors
- MeSH terms
- Endometriosis, Enzyme Activation, Female, Humans, Menstruation Disturbances, Prostaglandin-Endoperoxide Synthases, Prostaglandins, Receptors, Prostaglandin, Uterine Diseases, Signal Transduction, Endometrial Neoplasms
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