Aguilar-Rojas Arturo, Huerta-Reyes Maira
Research Unit in Reproductive Medicine, IMSS, Unidad Médica de Alta Especialidad (UMAE) en Ginecología y Obstetricia No. 4 Dr. Luis Castelazo Ayala, Sexto piso, 01090 México, D.F., Mexico.
Oncol Rep. 2009 Nov;22(5):981-90. doi: 10.3892/or_00000525.
Human gonadotropin-releasing hormone receptor (GnRHR) and its natural ligand human gonadotropin-releasing hormone (GnRH) were initially described as signaling complexes that play a key role in reproductive functions. By binding to specific receptors present on pituitary gonadotropes, GnRH regulates the sperm and ovum maturation, as well as steroidogenesis within the context of the hypothalamus-hypophysis axis. The expression of GnRH and its receptor has clearly been established in many extra-pituitary organs. Some of them are tumors from non-reproductive tissues such as liver, larynx, pancreas, colon, lymphoma, kidney, skin, blood and brain as well as tissues from reproductive track, for example ovary, endometrium, prostate and breast or tumors derived from these organs. Expression of GnRH and its receptor in these organs has gained much attention and several research groups have established their role during cell proliferation and cell motility. Although the signaling pathways and their effector proteins in these samples remain unclear, the molecular mechanism employed for GnRH and its receptor in extra-pituitary tissues could be related with non-classical GnRHR-signaling pathways. In the present review, we explore the vast literature reported on GnRH and GnRHR principally in tumors, describing how cross-talk between GnRHR and growth factor receptor, the coupling between GnRHR and many G proteins depending on cell context, and the regulation of several proteins associated with cell proliferation and cell motility are employed by GnRHR/GnRH to regulate their extra-pituitary activities.
人促性腺激素释放激素受体（GnRHR）及其天然配体人促性腺激素释放激素（GnRH）最初被描述为在生殖功能中起关键作用的信号复合物。通过与垂体促性腺细胞上存在的特定受体结合，GnRH在下丘脑 - 垂体轴的背景下调节精子和卵子的成熟以及类固醇生成。GnRH及其受体的表达已在许多垂体外器官中明确确立。其中一些是来自非生殖组织的肿瘤，如肝脏、喉部、胰腺、结肠、淋巴瘤、肾脏、皮肤、血液和大脑，以及来自生殖系统的组织，例如卵巢、子宫内膜、前列腺和乳腺或源自这些器官的肿瘤。GnRH及其受体在这些器官中的表达备受关注，几个研究小组已经确定了它们在细胞增殖和细胞运动中的作用。尽管这些样本中的信号通路及其效应蛋白仍不清楚，但GnRH及其受体在垂体外组织中所采用的分子机制可能与非经典的GnRHR信号通路有关。在本综述中，我们主要探讨了关于GnRH和GnRHR在肿瘤方面的大量文献，描述了GnRHR与生长因子受体之间的相互作用、GnRHR与许多G蛋白之间根据细胞环境的偶联，以及GnRHR / GnRH如何利用与细胞增殖和细胞运动相关的几种蛋白质来调节它们在垂体外的活性。
