Grant: Discovery Grants Program - Individual

This proposal is an extension of an on-going program of research on the physiology of growth hormone (GH) secretion and action. Although GH is mainly synthesized in somatotrophs cells of the pituitary gland, the applicant recently discovered that GH gene expression occurs in many extrapituitary tissues, including those that are sites of GH action. GH is thus likely to have autocrine or paracrine functions in addition to its endocrine roles. In the last cycle of NSERC support, the neural retina of the early chick embryo was shown to be both a site of GH production and GH action. Moreover, the expression of the GH gene in retinal ganglion cells (RGCs) was found to occur prior to that in the pituitary gland, providing a unique experimental model to differentiate between the local and systemic actions of GH in retinal development. By experimentally blocking GH synthesis in the neural retina, the applicant was thus able to establish that the expression of the GH gene in RGCs was of functional significance and involved in RGC survival during developmental waves of apoptosis and in RGC axon growth. In the current application the possibility that retinal GH is additionally involved in cell proliferation, migration and differentiation during early retinal development will be investigated, as will the possibility that it is involved in blood vessel formation and with the synapsing of the RGC axons to visual centers within the brain. The possibility that GH also modulates the electrophysiological signaling of RGCs will also be examined, as will the possibility that retinal GH is neuroprotective against glutamate-induced neurotoxicity. Finally, the factors regulating retinal GH secretion will be determined and compared with those regulating pituitary GH release. These studies will provide further understanding about retinal GH secretion they are likely to reveal hitherto unsuspected autocrine or paracrine roles of GH in retinal function.