GONADOTROPIN-RELEASING HORMONE ACTION

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 这些都是高度转化的研究，我们观察到突变性疾病的潜在基础通常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，这些突变受体可以被药物分子伴侣拯救并恢复功能。我们已经确定，路由的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，可以控制。在前一阶段，我们已经表明，错误折叠的hGnRHR可以重新折叠，使治疗药物不需要持续存在。我们还表明，hGnRHR的控制有助于解释这种受体对幅度和频率调制信号作出反应的能力的基本原理。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.