Physiological role and transmembranesignaling of gonadotropin-releasing hormonein granulosa cells : expression of Gn-RH and its receptor in the ovary

在颗粒细胞中，GnRH可刺激<32>磷酸参入磷脂酰肌醇（PtdIns），这种参入可被拮抗剂从其受体上取代结合的Gn-RH而终止，并被G1 n-RH重新占据而重新开始。在GnRH的抗FSH作用中也观察到antide的相同作用，FSH启动的芳香化酶活性被GnRH猝灭，当antide将GnRH从其受体上除去时，芳香化酶活性又重新启动。这两种反应与Gn-RH受体的占用提供了证据，有利于刺激PtdIns周转抑制芳香化酶激活的紧密耦合。综合这些资料，认为GnRH需要持续占据受体才能发挥作用，卵巢中的GnRH或GnRH样分泌物，除来自垂体外，也可能参与控制雄激素的合成， 关于我们 卵巢粘液囊腺癌和卵巢癌细胞系中Gn-RH的表达量分别为0.8 <plus-minus>± 0.12pg/mg蛋白和0.92 ± <plus-minus>0.17pg/mg蛋白，而正常卵巢和胎盘组织中均无表达。两个提取物样品从个别情况下诱发剂量依赖性磷脂酰肌醇在大鼠颗粒细胞类似于真正的Gn-RH. Gn-RHmRNA的破坏，检测到两个粘液囊腺癌标本，一个浆液囊腺癌，SK-OV-3细胞，但没有在无性细胞瘤，粘液囊腺瘤，正常卵巢和胎盘。高亲和力结合位点和非等摩尔范围的Gn-RHR mRNA的检出率高（90%以上）的标本中，子宫内膜癌（6/6）和子宫内膜癌（16/17），子宫肌瘤（6/6）和子宫肌瘤（4/5），上皮癌（21/23）和卵巢间质瘤（3/3）。在宫颈癌或生殖细胞驱动的卵巢肿瘤中没有大量的Gn-RHR。克隆细胞系的结果与在其各自的母体肿瘤中获得的结果相同。我们在广泛的子宫内膜和卵巢癌和组织中检测到Gn-RHR，但在子宫颈或生殖细胞来源的肿瘤中未检测到。Gn-RH受体的表达提高了Gn-RH可能在这些癌的生长中发挥直接调节作用的可能性，并为在这些恶性肿瘤中使用Gn-RH类似物的治疗方法提供了可能的攻击点。Gn-RH及其mRNA的表达提示Gn-RH可能在卵巢癌的生长中起自分泌调节作用。少

In granulosa cells, Gn-RH stimulated [^<32>P] phosphate incorporation into phosphatidylinositol (PtdIns) , which could be terminated by displacement of previously boundGn-RH from its receptor by antide and restarted by reoccupyingthe receptors with G1n-RH.Antide could rapidly prevent Gn-RH-stimulated PtdIns phosphorylation whenever it was added to incubations. An identical effect of antide was observed also in the anti-FSH action of Gn-RH.The aromatase activity initiated by FSH was quenched by Gn-RH and restarted at a time when Gn-RH was removed from its receptor by antide. These two responses associated with the occupancy of Gn-RH receptor provide the evidence in favor of a tight coupling of stimulated PtdIns turnover to suppression of aromatase activation. Taken together these data of requirement of continued occupancy of receptor for Gn-RH to exert its action, Gn-RH or Gn-RH-like hormonein ovaries, in addition to from pituitary, could participate in the control of steroidogenesis in … More the ovary in an autocrine or a paracrine manner.In human ovarian carcinomas surgically removed and human ovarian carcinoma cell lines, Gn-RH was shown to be present in extracts of ovarian mucinouscystadenocarcinoma sample (0.8<plus-minus>0.12pg/mgprotein) and ovarian adenocarcinoma cell line SK-OV-3 (0.92<plus-minus>0.17 pg/mgprotein) , but not in the normal ovary and placenta. Two of two extract samples from individual cases evoked dose-dependent phosphoinositide breakdown in rat granulosa cells similar to that caused by authentic Gn-RH.Gn-RH mRNA was detected in two of two mucinouscystadenocarcinoma specimens, one of one serouscystadenocarcinoma, and SK-OV-3cells, but not in the dysgerminoma, mucinouscystadenoma, and normal ovary and placenta. High affinity binding sites with nonomolar range of Kd and Gn-RHR mRNA were detected in a high proportion (over 90%) of the specimens from endometria (6 of 6) and endometrial carcinomas (16 of 17) , myometria (6 of 6) and myomas (4 of 5) , epithelial carcinoma (21 of 23) and stromal tumors (3 of 3) of the ovary. There was no substantial Gn-RHR in cervical carcinomas or germ cell-drived tumors of the ovary. Cloned cell lines gave identical results to those obtained in their respective mother tumWe detected Gn-RHR in a wide range of the carcinomas and tissues originating from the endometrium and ovary, but not in the uterine cervix or germ cell-derived tumors. The expression of Gn-RH receptor raises the possibility that Gn-RH may play a direct regulatory role in the growth of these carcinomas, and provides a possible point of attack for therapeutic approaches using Gn-RH analogs in these malignancies. The demonstration of Gn-RH and its mRNA raises the possibility that Gn-RH may play an autocrine regulatory role in the growth of ovarian carcinoma. Less