Author

Michelle Re

Date of Award

2008

Degree Type

Thesis

Degree Name

Master of Science

Program

Physiology

Supervisor

Dr. Andy Babwah

Abstract

The receptor for gonadotropin releasing hormone (GnRH-RI) is a G protein-coupled receptor (GPCR) that plays a key role in reproduction. Despite the clinical importance of the human GnRH-RI, studies defining basic properties of this receptor were lacking and this led me to characterize (i) the spatial characteristics of hGnRH-RI in a homologous (HTR-8∕SVneo) and heterologous (HEK 293) cell system, and (ii) the early signaling pathway to which GnRH-RI is coupled in HEK 293 cells. The first study revealed GnRH-RI is weakly expressed at the plasma membrane but strongly expressed on the nuclear membrane of both cell types, indicating that it is a nuclear GPCR. In the second study, I demonstrate that the plasma membrane-bound GnRH-RI/PKC-coupled signaling pathway regulates several PKC isoforms. Based on the responses of various isoforms following receptor activation, it appears that the isoforms may have both unique and redundant roles in regulating GnRH-RI signaling.

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