Anouar Y, Eiden L E
Section on Molecular Neuroscience, Laboratory of Cell Biology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, 20892, USA.
Neuroendocrinology. 1995 Dec;62(6):611-8. doi: 10.1159/000127057.
Expression of the neuropeptide galanin in the adrenal gland is rapidly induced by reflex stimulation of the splanchnic nerve following insulin-induced hypoglycemia. Here, we examine the cellular localization and mechanism of galanin mRNA upregulation in the adrenal gland after insulin administration, by Northern blot and in situ histochemical hybridization analysis. A 5- to 16-fold increase in galanin mRNA levels, measured by Northern blot hybridization using a rat galanin cRNA probe, was observed after insulin-induced hypoglycemia. An increase in galanin mRNA levels could be detected as early as two hours after administration of a single dose (10 U/kg) of insulin (Iletin II), consistent with the increase in galanin peptide levels in the adrenal gland within 24 h of insulin shock. Insulin-induced galanin mRNA upregulation was confined to the rat adrenal: neither hypothalamic nor pituitary levels of GAL mRNA were altered by insulin treatment. Adrenal galanin mRNA levels were maximally increased by 4 h, remained maximally elevated for at least 48 h, and had returned to baseline 6 days after insulin administration. In situ hybridization analysis localized galanin mRNA induction to scattered groups of chromaffin cells throughout the medulla. These data demonstrate that regulation of GAL biosynthesis in the adrenal medulla occurs at a pretranslational level, and in a subpopulation of chromaffin cells. Rapid and robust upregulation of galanin biosynthesis in chromaffin cells upon insulin-induced splanchnic nerve stimulation suggests a hormonal or paracrine role for galanin in the adrenomedullary response to hypoglycemic shock.
胰岛素诱导低血糖后,内脏神经的反射刺激可迅速诱导肾上腺中神经肽甘丙肽的表达。在此,我们通过Northern印迹和原位组织化学杂交分析,研究胰岛素给药后肾上腺中甘丙肽mRNA上调的细胞定位和机制。使用大鼠甘丙肽cRNA探针通过Northern印迹杂交测量,胰岛素诱导低血糖后观察到甘丙肽mRNA水平增加了5至16倍。单次注射(10 U/kg)胰岛素(胰岛素II)后两小时即可检测到甘丙肽mRNA水平升高,这与胰岛素休克后24小时内肾上腺中甘丙肽肽水平的增加一致。胰岛素诱导的甘丙肽mRNA上调仅限于大鼠肾上腺:胰岛素治疗未改变下丘脑或垂体的GAL mRNA水平。肾上腺甘丙肽mRNA水平在4小时时最大程度增加,至少48小时保持最大升高状态,胰岛素给药6天后恢复到基线水平。原位杂交分析将甘丙肽mRNA诱导定位到整个髓质中分散的嗜铬细胞群。这些数据表明,肾上腺髓质中GAL生物合成的调节发生在翻译前水平,且在嗜铬细胞的一个亚群中。胰岛素诱导内脏神经刺激后嗜铬细胞中甘丙肽生物合成的快速且强烈上调表明,甘丙肽在肾上腺髓质对低血糖休克的反应中具有激素或旁分泌作用。