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.
Mol Hum Reprod. 2011 Sep;17(9):587-93. doi: 10.1093/molehr/gar020. Epub 2011 Mar 30.
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.
尿皮质素 2（Ucn 2）和尿皮质素 3（Ucn 3）是由人子宫内膜表达的神经肽。本研究评估了（i）Ucn 2 和 Ucn 3 mRNA 在子宫内膜异位症病变和子宫内膜异位症妇女的子宫内膜中的表达；（ii）Ucn 2 和 Ucn 3 对培养的子宫内膜基质细胞细胞因子分泌的影响。从子宫内膜瘤（n=39）中收集子宫内膜异位组织；在整个月经周期中，从患有（n=39）和不患有（n=41）子宫内膜异位症的妇女中获得子宫内膜标本。分析组织标本中 Ucn 2 和 Ucn 3 mRNA 的表达和肽定位；研究了 Ucn 2 或 Ucn 3 对培养的子宫内膜基质细胞肿瘤坏死因子（TNF-α）和白细胞介素（IL-4）分泌的影响。通过 RT-PCR 和免疫组织化学分别评估 Ucn 2 和 Ucn 3 mRNA 的表达和定位；通过 ELISA 测量细胞因子分泌。结果表明，子宫内膜异位组织表达 Ucn 2 和 Ucn 3，异位内膜中 Ucn 3 的表达高于在位内膜。对照组子宫内膜 Ucn 2 mRNA 的表达在早期增殖期达到峰值，而在子宫内膜异位症患者中，整个月经周期的表达水平较低且无明显变化。对照组子宫内膜 Ucn 3 mRNA 的表达在晚期分泌期最高，而在子宫内膜异位症患者中，水平较低且无月经周期相关变化。当添加到培养的子宫内膜细胞培养物中时，Ucn 2 显著增加 TNF-α（P<0.01）和 IL-4（P<0.001），而 Ucn 3 诱导 IL-4 分泌增加（P<0.01）。总之，子宫内膜异位组织表达和定位 Ucn 2 和 Ucn 3；子宫内膜异位症患者在位子宫内膜的 Ucn 2 和 Ucn 3 mRNA 表达低于对照组，且无子宫内膜周期相关变化。Ucn 2 和 Ucn 3 调节培养的子宫内膜细胞中 TNF-α和 IL-4 的分泌。这些数据表明 Ucn 2 和 Ucn 3 可能参与子宫内膜异位症的发病机制。
