PDF(Pubmed)
Abstract：
Ventromedial hypothalamic nucleus (VMN) growth hormone-releasing hormone (Ghrh) neurotransmission shapes counterregulatory hormone secretion. Dorsomedial VMN Ghrh neurons express the metabolic-sensitive transcription factor steroidogenic factor-1/NR5A1 (SF-1). In vivo SF-1 gene knockdown tools were used here to address the premise that in male rats, SF-1 may regulate basal and/or hypoglycemic patterns of Ghrh, co-transmitter biosynthetic enzyme, and estrogen receptor (ER) gene expression in these neurons. Single-cell multiplex qPCR analyses showed that SF-1 regulates basal profiles of mRNAs that encode Ghrh and protein markers for neurochemicals that suppress (γ-aminobutyric acid) or enhance (nitric oxide; glutamate) counterregulation. SF-1 siRNA pretreatment respectively exacerbated or blunted hypoglycemia-associated inhibition of glutamate decarboxylase67 (GAD67/GAD1) and -65 (GAD65/GAD2) transcripts. Hypoglycemia augmented or reduced nitric oxide synthase and glutaminase mRNAs, responses that were attenuated by SF-1 gene silencing. Ghrh and Ghrh receptor transcripts were correspondingly refractory to or increased by hypoglycemia, yet SF-1 knockdown decreased both gene profiles. Hypoglycemic inhibition of ER-alpha and G protein-coupled-ER gene expression was amplified by SF-1 siRNA pretreatment, whereas as ER-beta mRNA was amplified. SF-1 knockdown decreased (corticosterone) or elevated [glucagon, growth hormone (GH)] basal counterregulatory hormone profiles, but amplified hypoglycemic hypercorticosteronemia and -glucagonemia or prevented elevated GH release. Outcomes document SF-1 control of VMN Ghrh neuron counterregulatory neurotransmitter and ER gene transcription. SF-1 likely regulates Ghrh nerve cell receptivity to estradiol and release of distinctive neurochemicals during glucose homeostasis and systemic imbalance. VMN Ghrh neurons emerge as a likely substrate for SF-1 control of glucose counterregulation in the male rat.
摘要：
下丘脑腹内侧核（VMN）生长激素释放激素（Ghrh）神经传递形成反调节激素分泌。背侧VMNGhrh神经元表达代谢敏感转录因子类固醇生成因子1/NR5A1（SF-1）。体内SF-1基因敲除工具用于解决在雄性大鼠中,SF-1可以调节Ghrh的基础和/或低血糖模式，生物合成酶，和雌激素受体（ER）基因在这些神经元中的表达。单细胞多重qPCR分析显示，SF-1调节编码Ghrh的mRNA的基础谱和抑制（γ-氨基丁酸）或增强（一氧化氮；谷氨酸）反调节的神经化学物质的蛋白质标记。SF-1siRNA预处理分别加剧或减弱了与低血糖相关的谷氨酸脱羧酶67（GAD67/GAD1）和-65（GAD65/GAD2）转录本的抑制。低血糖增加或减少一氧化氮合酶和谷氨酰胺酶mRNA，通过SF-1基因沉默减弱的反应。Ghrh和Ghrh受体转录物相应地对低血糖难治或增加，然而SF-1敲低降低了两个基因谱。通过SF-1siRNA预处理扩增对ER-α和G蛋白偶联ER基因表达的降血糖抑制作用,而ER-βmRNA扩增。SF-1敲低降低（皮质酮）或升高[胰高血糖素，生长激素（GH）]基础反调节激素谱，但增加了低血糖的高皮质激素血症和-胰高血糖素血症或阻止了GH释放的升高。结果记录了SF-1对VMNGhrh神经元反调节神经递质和ER基因转录的控制。SF-1可能在葡萄糖稳态和全身失衡期间调节Ghrh神经细胞对雌二醇的接受性和独特神经化学物质的释放。在雄性大鼠中，VMNGhrh神经元可能是SF-1控制葡萄糖反调节的底物。
