Urocortin 2 and urocortin 3 in endometriosis: evidence for a possible role in inflammatory response
Open accessAbstract
Urocortin 2 (Ucn 2) and urocortin 3 (Ucn 3) are neuropeptides expressed by human endometrium. This study evaluated (i) the expression of Ucn 2 and Ucn 3 mRNA in endometriotic lesions and in endometrium of women with endometriosis; (ii) the effect of Ucn 2 and Ucn 3 on cytokines secretion from cultured endometrial stromal cells. Endometriotic tissue was collected from endometrioma (n=39); endometrial specimens were obtained from women with (n=39) and without (n=41) endometriosis throughout menstrual cycle. Tissue specimens were analysed for Ucn 2 and Ucn 3 mRNA expression and peptide localization; the effects of Ucn 2 or Ucn 3 on tumour necrosis factor (TNF-α) and interleukin (IL-4) secretion from cultured endometrial stromal cells was studied. Ucn 2 and Ucn 3 mRNA expression and localization were assessed by RT-PCR and by immuohistochemistry, respectively; cytokines secretion were measured by ELISA. Results showed that endometriotic tissue expressed both Ucn 2 and Ucn 3, with Ucn 3 expression higher in ectopic than in eutopic endometrium. Endometrial Ucn 2 mRNA expression in controls showed peak values at early proliferative phase, while in endometriotic patients low expression and no significant changes throughout menstrual cycle were observed. Endometrial Ucn 3 mRNA expression was highest in late secretory phase in controls, while in endometriotic patients low levels and no menstrual-cycle-related changes were found. When added to cultured endometrial cell cultures, Ucn 2 significantly increased TNF-α (P<0.01) and IL-4 (P<0.001), while Ucn 3 induced an increase of IL-4 secretion (P<0.01). In conclusion, endometriotic tissue expressed and localized Ucn 2 and Ucn 3; patients with endometriosis showed Ucn 2 and Ucn 3 mRNA expression in eutopic endometrium lower than in control group, with no endometrial cycle-related changes. Ucn 2 and Ucn 3-modulated TNF-α and IL-4 secretion from culture endometrial cells. These data suggest a possible involvement of Ucn 2 and Ucn 3 in the mechanisms of endometriosis.
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An involvement of the stress pathway in inflammation in endometriosis is suggested.
“an involvement of this stress pathway in inflammation is suggested [110].”
From Hormonal treatments for endometriosis: The endocrine background (2022) · cites this paper as [110]
Endometriotic tissue expresses both Ucn 2 and Ucn 3, which modulate TNF-α and IL-4 secretion.
“endometriotic tissue expresses both Ucn 2 and Ucn 3 (which modulate TNF-α and IL-4 secretion)”
From Hormonal treatments for endometriosis: The endocrine background (2022) · cites this paper as [110]
CRH and Ucn significantly increase COX2 expression, and this effect is reversed by the CRH-R2 antagonist astressin.
“CRH and Ucn significantly increase COX2 expression (effect was reversed by the CRH-R2 antagonist astressin)”
From Hormonal treatments for endometriosis: The endocrine background (2022) · cites this paper as [110]
The results on cultured endometrial stromal cells (p. 4) report that Ucn 2 and Ucn 3 increased TNFα or IL-4 secretion and that the CRH-R2 antagonist ast2b counteracted those effects. The passages found for COX2, CRH, and astressin do not address whether CRH or Ucn increases COX2 expression or whether an antagonist reverses that effect. (LLM, conf=0.75)
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Hormonal treatments for endometriosis: The endocrine background
Vannuccini, S., Clemenza, S., Rossi, M., & Petraglia, F. (2022) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-021-09666-w · Cited by 336 · see citing works
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- Authors
- Novembri, R., Carrarelli, P., Toti, P., Rocha, A. L. L., Borges, L. E., Reis, F. M., Piomboni, P., Florio, P., & Petraglia, F.
- Affiliations
- University of Siena (IT)
- Universidade Federal de Minas Gerais (BR)
- Corresponding author
- Petraglia, F.
- Venue
- Molecular Human Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-03-30
- Volume
- 17
- Issue
- 9
- Pages
- 587-593
- ISSN
- 1360-9947 (ISSN-L)
- 1460-2407
- OpenAlex
- W2165383892
- Cited by
- 41
- References
- 48
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 7 · 2020: 2 · 2019: 4 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 7 · 2012: 1
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Human Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Plant and fungal interactions
- Keywords
- urocortin 2, urocortin 3, endometriosis, endometrioma, neuropeptides, endometrial stromal cells, TNF-α, IL-4, inflammation, menstrual cycle, eutopic endometrium, ectopic endometrium, cytokine production, mRNA expression, endometriosis pathogenesis
- MeSH terms
- Adult, Cells, Cultured, Corticotropin-Releasing Hormone, Endometriosis, Endometrium, Female, Humans, Inflammation, Menstrual Cycle, Tissue Distribution, Tumor Necrosis Factor-alpha, Interleukin-4, Stromal Cells, Urocortins, Young Adult
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