The Gnrh Receptor-Associated Membrane Raft Proteome In Mouse Gonadotrope Cells
Gonadotropin releasing hormone (GnRH) is the central hormone of reproduction in vertebrates. This hormone is secreted from the hypothalamus in response to environmental, steroid hormone feedback and other stimuli in a pulsatile manner and travels via the hypophyseal portal vasculature to the anterior pituitary. GnRH binding to its receptor on the surface of pituitary gonadotropes stimulates the release of the gonadotropin hormones: luteinizing hormone (LH) and follicle stimulating hormone (FSH), heterodimers of the common [alpha] subunit with the hormone-specific [beta] subunits. In addition to secretion of gonadotropin hormones, GnRH stimulates the transcription of the gonadotropin subunit genes and that of its own receptor (GnRHR). The GnRHR has been shown in recent years to be a constitutive occupant of membrane raft microdomains within the plasma membrane. GnRHR association with these microdomains appears to be required for the initiation of downstream signaling processes within the GnRH signaling network including activation of the mitogenactivated protein kinase, extracellular signal regulated kinase (ERK). GnRHR-induced ERK activation is absolutely required for gonadotropin subunit gene expression and fertility in mice. In this dissertation the components of the GnRHR-associated membrane raft microdomain are explored providing insight into how the receptor might be connected to membrane microdomains, the actin cytoskeletal network, and the initiation of downstream transcriptional events. These studies introduce the flotillin/reggie proteins and [beta] catenin as novel members of the GnRHR-associated membrane raft proteome in addition to identifying a list of proteins for future studies.
Gonadotropin Releasing Hormone Receptor; Proteomic; Membrane Raft
Roberson, Mark Stephen
Brown, William J; Collins, Ruth N.
Ph. D., Veterinary Medicine
Doctor of Philosophy
dissertation or thesis