GnRH II as a possible cytostatic regulator in the development of endometriosis
GnRH II as a possible cytostatic regulator in the development of endometriosis
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DOI：
10.1093/humrep/dei192
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发表时间：
2005-11-01
影响因子：
6.1
通讯作者：
Taketani, Y
中科院分区：
文献类型：
--
作者：
Morimoto, C;Osuga, Y;Taketani, Y
背景技术背景：GnRH II是GnRH的第二种形式，广泛分布于女性生殖道的外周组织以及中枢神经系统。在本研究中，我们研究了GnRH II在子宫内膜异位症中的可能意义。方法：观察GnRH Ⅱ对体外培养的兔骨髓基质细胞摄取5-溴-2 '-脱氧尿苷（BrdU）的影响。还研究了GnRH II对白细胞介素（IL）-1 β诱导的环氧合酶（考克斯）-2和IL-8表达的影响。采用实时荧光定量RT-PCR法检测子宫内膜组织中GnRH I、GnRH II、GnRH I型受体和GnRH II型受体mRNA水平。结果：GnRH II剂量依赖性地抑制子宫内膜间质细胞对BrdU的摄取。用IL-1 β处理显著增加子宫内膜间质细胞中考克斯-2和IL-8的mRNA水平以及这些细胞分泌IL-8蛋白，而这些增量被补充GnRH II显著抑制。在子宫内膜异位症患者的子宫内膜和子宫内膜异位症组织中，GnRH II的mRNA水平低于无子宫内膜异位症患者的子宫内膜组织，无论是在增殖期还是分泌期。此外，对于GnRH I、I型GnRH受体和II型GnRH受体，在分泌期子宫内膜异位症患者的子宫内膜组织中的mRNA水平低于非子宫内膜异位症患者。结论：鉴于GnRH II对子宫内膜间质细胞的抗增殖和抗炎作用，子宫内膜异位症患者在位和异位子宫内膜中GnRH II的表达较低，表明内源性GnRH II介导的细胞生长抑制调节可能在子宫内膜异位症的发展中受损。
BACKGROUND: GnRH II is the second form of GnRH and is widely distributed in peripheral tissues of the female reproductive tract as well as in the central nervous system. In the present study, we studied the possible implication of GnRH II in endometriosis. METHODS: Effects of GnRH II on 5-bromo-2'-deoxyuridine (BrdU) uptake by cultured endometriotic stromal cells were examined. Effects of GnRH II on interleukin (IL)-1 beta-induced expression of cyclooxygenase (COX)-2 and IL-8 were also studied. mRNA levels of GnRH I, GnRH II, type I GnRH receptor and type II GnRH receptor were determined by real-time quantitative RT-PCR in endometrial tissues of women with or without endometriosis and in endometriotic tissues. RESULTS: GnRH II dose-dependently suppressed BrdU uptake by endometrial stromal cells. Treatment with IL-1 beta markedly increased mRNA levels of COX-2 and IL-8 in endometrial stromal cells and IL-8 protein secretion by these cells, while these increments were significantly suppressed by supplementation with GnRH II. The mRNA levels of GnRH II were lower in endometrial and endometriotic tissues of women with endometriosis than in endometrial tissues of women without endometriosis, both in the proliferative phase and the secretory phase. In addition, as for GnRH I, type I GnRH receptor and type II GnRH receptor, the mRNA levels were lower in endometrial tissues of women with endometriosis than in those without endometriosis in the secretory phase. CONCLUSIONS: In the light of the demonstrated antiproliferative and anti-inflammatory effects of GnRH II on endometrial stromal cells, the lower expression of GnRH II in eutopic and ectopic endometrium of women with endometriosis suggests that endogenous GnRH II-mediated cytostatic regulation may be impaired in the development of endometriosis.