Growth Hormone Promotes Axon Growth in the Developing Nervous System
Growth Hormone Promotes Axon Growth in the Developing Nervous System
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DOI：
10.1210/en.2008-1242
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发表时间：
2009-06-01
期刊：
影响因子：
4.8
通讯作者：
Harvey, Steve
中科院分区：
文献类型：
--
作者：
Baudet, Marie-Laure;Rattray, Darrien;Harvey, Steve
出生后，内分泌GH主要由垂体生长激素产生。然而，生长激素也在头外部位产生，包括发育中的神经系统组织，如神经视网膜。尽管生长激素在神经系统中的作用开始显现，但它们在很大程度上仍是未知的。我们发现，在胚胎日(E) 4-12的鸡胚胎中，神经视网膜中的生长激素主要存在于视网膜神经节细胞（RGCs）的轴突中，但在胚胎日(E) 14-18时不再存在。这个时间窗口对应于RGC轴突生长的时期。在E7 RGC层细胞中也检测到GH受体mRNA， GH受体蛋白在RGC轴突中与GH共定位。因此研究了生长激素促进轴突生长的可能性。外源性GH诱导经免疫计划纯化的E7 RGC培养物在10（-9）和10(-6)M处轴突伸长显著增加。使用RNA干扰介导的基因沉默来检测内源性生长激素是否类似地改变轴突的生长。我们首先在LacZ-cGH表达质粒上用HEK细胞测试了GH小干扰RNA抑制GH的能力，发现其抑制能力达到90%。将GH小干扰RNA转染到免疫修饰的RGC培养物中，检测到内源性GH下调63%，RGC轴突长度减少40%。综上所述，这些数据表明生长激素作为一种自分泌或旁分泌信号分子，促进发育中的神经组织，即小鸡胚胎的神经视网膜的轴突生长。（内分泌学150:2758-2766,2009）
Postnatally, endocrine GH is primarily produced by pituitary somatotrophs. GH is, however, also produced in extrapituitary sites, including tissues of the developing nervous system such as the neural retina. Whereas GH roles in the nervous system are starting to emerge, they are still largely unknown. We show here that GH in the neural retina is mainly present in the axons of retinal ganglion cells (RGCs) in embryonic day (E) 4-12 chick embryos, but it is no longer present at E14-18. This temporal window corresponds to the period of RGC axon growth. GH receptor mRNA was also detected within cells of the E7 RGC layer and GH receptor protein colocalized with GH in RGC axons. The possibility that GH promotes axon growth was thus investigated. Exogenous GH induced a significant increase in axon elongation at 10(-9) and 10(-6) M in E7 RGC culture purified by immunopanning. RNA interference-mediated gene silencing was used to examine whether endogenous GH similarly alters axon outgrowth. The ability of GH small-interfering RNA to knock down GH was first tested using HEK cells on a LacZ-cGH expression plasmid and found to reach 90%. Upon transfection of GH small-interfering RNA to immunopanned RGC culture, a 63% knockdown of endogenous GH was detected and RGC axon length was found to be reduced by 40%. Taken together, these data suggest that GH acts as an autocrine or paracrine signaling molecule to promote axon growth in a developing nervous tissue, the neural retina of chick embryos. (Endocrinology 150: 2758-2766, 2009)