Department of Biological Sciences, School of Science, The University of Tokyo, Bunkyo, Tokyo 113-0033, Japan.
Gen Comp Endocrinol. 2013 Jan 15;181:259-64. doi: 10.1016/j.ygcen.2012.09.023. Epub 2012 Sep 29.
GnRH was originally identified as a hypothalamic factor which promotes gonadotropin release from the pituitary and was named gonadotropin-releasing hormone (GnRH). However, broad tissue distributions of GnRH and the GnRH receptor in various extrapituitary tissues and organs have been revealed and it has been suggested that GnRH has extrapituitary effects such as neuromodulation, immunomodulation, and regulation of follicular atresia and ovulation. Although a number of studies have been performed on these effects, little is known about the molecular mechanisms and physiological settings in which GnRH exerts its activities in extrapituitary organs or tissues. Our recent studies had demonstrated that GnRH is able to regulate both cell proliferation and cell migration at much lower concentration than that in the peripheral circulation by using human carcinoma cell lines. Moreover, stimulating activity of GnRH on the developing chick embryonic GnRH neurons was also demonstrated and strongly suggests possible involvement of GnRH in some of extrapituitary functions. This mini-review intends to provide solid evidence of GnRH activity in the regulation of cell proliferation and migration and its physiological relevance in extra-pituitary functions. Recent other research, including that in various invertebrates, provides new insight into the evolutionary scenarios of GnRH signaling systems, and GnRH functions. Both proliferating and migrating activities are important fundamental cellular activities and could provide an important clue into understanding what the driving force behind the evolution of the GnRH signaling system was.
促性腺激素释放激素最初被鉴定为一种下丘脑因子，可促进垂体释放促性腺激素，因此被命名为促性腺激素释放激素（GnRH）。然而，在各种垂体外组织和器官中，GnRH 和 GnRH 受体广泛存在，这表明 GnRH 具有垂体外作用，如神经调节、免疫调节以及卵泡闭锁和排卵的调节。尽管已经对这些作用进行了大量研究，但对于 GnRH 在垂体外器官或组织中发挥作用的分子机制和生理环境知之甚少。我们最近的研究表明，使用人癌细胞系，GnRH 能够以比外周循环中低得多的浓度调节细胞增殖和细胞迁移。此外，还证明了 GnRH 对发育中的鸡胚 GnRH 神经元的刺激活性，这强烈表明 GnRH 可能参与了一些垂体外功能。这篇小型综述旨在提供 GnRH 在调节细胞增殖和迁移中的活性及其在垂体外功能中的生理相关性的确凿证据。最近的其他研究，包括在各种无脊椎动物中的研究，为 GnRH 信号系统和 GnRH 功能的进化情景提供了新的见解。增殖和迁移活动都是重要的基本细胞活动，这可能为理解 GnRH 信号系统进化的驱动力提供了重要线索。
