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，Gn-RH刺激[^<32>P]磷酸结合到磷脂酰肌醇（PtdIns）中，这种结合可以通过抗原将先前结合的Gn-RH从其受体中置换而终止，并通过G1n-RH重新占据受体而重新开始。无论何时加入Antide，它都能迅速阻止gn - rh刺激的PtdIns磷酸化。在Gn-RH的抗fsh作用中也观察到相同的效果。由FSH启动的芳香酶活性被Gn-RH猝灭，并在Gn-RH被抗原从其受体中移除时重新启动。这两种与Gn-RH受体占用相关的反应提供了支持受刺激的PtdIns周转与抑制芳香化酶激活紧密耦合的证据。综上所述，Gn-RH或Gn-RH样激素除了来自垂体外，还可能以自分泌或旁分泌的方式参与卵巢甾体生成的控制。在手术切除的人卵巢癌和人卵巢癌细胞系中，Gn-RH存在于卵巢粘液囊腺癌样品（0.8<正负>0.12pg/mg蛋白）和卵巢腺癌细胞系SK-OV-3（0.92<正负>0.17 pg/mg蛋白）的提取物中，但不存在于正常卵巢和胎盘中。来自个别病例的两种提取物样品中的两种在大鼠颗粒细胞中引起剂量依赖性磷酸肌肽分解，类似于真正的Gn-RH引起的分解。在两个粘液囊腺癌标本中的两个、一个浆液囊腺癌标本中的一个和sk - ov -3细胞中检测到Gn-RH mRNA，但在无生殖细胞瘤、粘液囊腺瘤和正常卵巢和胎盘中未检测到Gn-RH mRNA。在子宫内膜（6 / 6）和子宫内膜癌（17 / 16）、子宫肌分症（6 / 6）和肌瘤（5 / 4）、上皮癌（23 / 21）和卵巢间质瘤（3 / 3）的标本中，检测到高亲和力结合位点（Kd和Gn-RHR mRNA的单摩尔范围）的比例很高（超过90%）。在宫颈癌和卵巢生殖细胞驱动的肿瘤中没有大量的Gn-RHR。克隆细胞系的结果与在各自的母体肿瘤中获得的结果相同。我们在子宫内膜和卵巢的多种癌和组织中检测到Gn-RHR，但在子宫颈或生殖细胞衍生的肿瘤中没有检测到。Gn-RH受体的表达提高了Gn-RH可能在这些肿瘤的生长中起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的表达表明，Gn-RH可能在卵巢癌的生长过程中发挥自分泌调节作用。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