Caunt Christopher J, Armstrong Stephen P, McArdle Craig A
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (LINE), Department of Clinical Sciences at South Bristol, University of Bristol, Bristol, UK.
Methods Mol Biol. 2010;661:507-24. doi: 10.1007/978-1-60761-795-2_32.
Gonadotrophin-releasing hormone (GnRH) is a hypothalamic peptide that acts via G(q/11)-coupled 7TM receptors on pituitary gonadotrophs and mediates the central control of reproduction. Recent evidence also indicates that GnRH can affect numerous tissues, but the molecular mechanisms of GnRH receptor stimulation are cell type-specific. Extracellular signal-regulated kinase (ERK) 1 and 2 are key regulators of GnRH function in several cell types, but they also integrate signals from a wide variety of other stimuli. This leads to the obvious question of how specific cellular responses to ERK activation occur, and it is now clear that this is, in part, achieved through strict spatiotemporal control of ERK activity. This means that, in order to infer the function of ERK regulation accurately, multiple readouts for ERK activity, localisation and downstream consequences (e.g. transcriptional activation or cell growth) must be compared simultaneously. Here, we describe some of our findings in the investigation of GnRH signalling to ERK, with particular emphasis on novel, high-content microscopy methods for studying ERK regulation.
促性腺激素释放激素（GnRH）是一种下丘脑肽，它通过与G（q/11）偶联的7次跨膜受体作用于垂体促性腺细胞，介导生殖的中枢控制。最近的证据还表明，GnRH可影响多种组织，但GnRH受体刺激的分子机制具有细胞类型特异性。细胞外信号调节激酶（ERK）1和2是几种细胞类型中GnRH功能的关键调节因子，但它们也整合来自多种其他刺激的信号。这就引出了一个明显的问题，即细胞如何对ERK激活产生特异性反应，现在很清楚，这部分是通过对ERK活性的严格时空控制来实现的。这意味着，为了准确推断ERK调节的功能，必须同时比较ERK活性、定位和下游后果（如转录激活或细胞生长）的多个读数。在这里，我们描述了我们在研究GnRH向ERK信号传导方面的一些发现，特别强调了用于研究ERK调节的新型高内涵显微镜方法。
