Urocortin 2 and urocortin 3 in endometriosis: evidence for a possible role in inflammatory response

Novembri R, Romina Novembri, Carrarelli P, Patrizia Carrarelli, Paolo Toti, Ana Luiza L Rocha, Ana Luiza Lunardi Rocha, Lavinia E Borges, Lavínia E. Borges, Borges LE, Fernando M. Reis, Paola Piomboni, Piomboni P, Pasquale Florio, Florio P, Felice Petraglia
Molecular human reproduction · 2011 · vol. 17(9) , pp. 587–593 · doi:10.1093/molehr/gar020 · PMID:21454316 · W2165383892
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Urocortin 2 and 3 are expressed in endometriotic lesions and modulate inflammatory cytokine secretion from endometrial cells, suggesting a role in endometriosis pathogenesis.

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Abstract

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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Condition tags

endometriosisendometrioma

MeSH descriptors

Corticotropin-Releasing Hormone Endometriosis Endometriosis Inflammation Urocortins Adult Adult Cells, Cultured Cells, Cultured Corticotropin-Releasing Hormone Corticotropin-Releasing Hormone Corticotropin-Releasing Hormone Corticotropin-Releasing Hormone Endometriosis Endometriosis Endometrium Endometrium Endometrium Endometrium Endometrium

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