title: Urocortin 2 and urocortin 3 in endometriosis: evidence for a possible role in inflammatory response.
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.
authors: Department of Pediatrics, Obstetrics and Reproductive Medicine, Section of Obstetrics and Gynecology, University of Siena, Policlinico Santa Maria alle Scotte Viale Bracci, Siena 53100, Italy.
authors: Romina
authors: R
authors: Novembri
authors: Patrizia
authors: P
authors: Carrarelli
authors: Paolo
authors: P
authors: Toti
authors: Ana Luiza L
authors: AL
authors: Rocha
authors: Lavinia E
authors: LE
authors: Borges
authors: Fernando M
authors: FM
authors: Reis
authors: Paola
authors: P
authors: Piomboni
authors: Pasquale
authors: P
authors: Florio
authors: Felice
authors: F
authors: Petraglia
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology*; D004717:Endometrium / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D015847:Interleukin-4 / Q000378:metabolism; D008597:Menstrual Cycle / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D054832:Urocortins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D014409:Tumor Necrosis Factor-alpha; C426705:UCN2 protein, human; C426704:UCN3 protein, human; D054832:Urocortins; D015847:Interleukin-4; D003346:Corticotropin-Releasing Hormone