GONADOTROPIN-RELEASING HORMONE ACTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在这些高度翻译的研究中，我们观察到突变疾病的潜在基础往往是其他功能蛋白质的错误路由，在这种情况下，是受体，但其他实验室现在已经证实了其他受体、离子通道和酶的这一点。我们已经证明，这些突变的受体可以被药理伴侣拯救并恢复功能。我们已经确定，路由调节也是一种正常类型的翻译后调节，发生在常规细胞功能中，并且是可以控制的。在前一阶段，我们已经证明了错误折叠的hGnRHR可以重新折叠，因此不需要持续存在治疗剂。我们还表明，对hGnRHR的控制有助于解释该受体对幅度和频率调制信号做出反应的基本能力。对GnRHR类似物进行了潜在治疗作用的筛选，并发表了一篇综述。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. These are highly translational studies in which we have observed that the underlying basis of mutational disease is frequently the mis-routing of otherwise functional proteins, in this case a receptorbut other labs have now confirmed this for other receptors, ion channels and enzymes. We have shown that these mutant receptors can be rescued and restored to function by pharmacological chaperones. We have determined that the regulation of routing is also a normal type of post-translational regulation that occurs in routine cell function and can be controlled. During the prior period we have shown that misfolded hGnRHR can be refolded so that therapeutic agents need not be continuously present. We have also shown that control of hGnRHR helps explain the basics of the ability of this receptor to respond to both amplitude and frequency modulated signals. GnRHR analogs were screened for potential therapeutic action and a review was published.