Growth hormone: an autocrine/paracrine in retinal function

生长激素：视网膜功能中的自分泌/旁分泌

• 批准号: 3617-2013
• 负责人: Harvey, Stephen
• 金额: $ 2.4万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=592762
• 关键词: Growth; hormone; autocrine; paracrine; retinal

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.

这一建议是对生长激素（GH）分泌和作用的生理研究正在进行的计划的延伸。虽然生长激素主要在垂体的生长生长细胞中合成，但申请人最近发现，生长激素基因在许多垂体外组织中也有表达，包括那些生长激素的作用部位。因此，生长激素除了其内分泌作用外，还可能具有自分泌或旁分泌功能。在NSERC支持的最后一个周期中，早期鸡胚胎的神经视网膜被证明是生长激素产生和生长激素作用的场所。此外，研究发现生长激素基因在视网膜神经节细胞（rgc）中的表达先于垂体的表达，这为区分生长激素在视网膜发育中的局部和全身作用提供了一个独特的实验模型。通过实验阻断神经视网膜中的生长激素合成，申请人因此能够确定生长激素基因在RGC中的表达具有功能意义，并参与RGC在凋亡发育波和RGC轴突生长期间的存活。在目前的应用中，将研究视网膜生长激素在早期视网膜发育过程中参与细胞增殖、迁移和分化的可能性，以及它参与血管形成和RGC轴突与大脑视觉中心突触的可能性。还将研究生长激素调节rgc的电生理信号的可能性，以及视网膜生长激素对谷氨酸诱导的神经毒性具有神经保护作用的可能性。最后，确定调节视网膜生长激素分泌的因素，并与调节垂体生长激素释放的因素进行比较。这些研究将提供对视网膜生长激素分泌的进一步了解，它们可能揭示迄今为止未被怀疑的生长激素在视网膜功能中的自分泌或旁分泌作用。