GONADOTROPIN-RELEASING HORMONE ACTION

促性腺激素释放激素作用

• 批准号: 8357723
• 负责人: P. MICHAEL CONN
• 金额: $ 3.63万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357723
• 关键词: Cell physiology; Disease; Enzymes; Frequencies; Funding; Gonadotropin Hormone Releasing Hormone; Gonadotropin-Releasing Hormone Receptor; Grant; Human; Ion Channel; Molecular; Molecular Chaperones; National Center for Research Resources; Post-Translational Regulation; Primates; Principal Investigator; Proteins; Publishing; Regulation; Research; Research Infrastructure; Resources; Signal Transduction; Source; Therapeutic; Therapeutic Agents; United States National Institutes of Health; analog; base; cost; mutant; receptor; translational study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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 the gonadotropin releasing hormone (GnRH) receptor (R)-but others have now confirmed this for additional 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 human (h) GnRHR can be refolded so that therapeutic agents need not be continuously present. We have also shown that control of hGnRHR helps explain 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 and the molecular mechanism of pharmacoperone action was established.

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