类固醇生成因子-1 对雄性大鼠下丘脑背内侧核 Ghrh 神经元递质标记和雌激素受体基因表达的调控

IF 3.9 4区 医学 Q2 NEUROSCIENCES
ASN NEURO Pub Date : 2024-01-01 Epub Date: 2024-07-15 DOI:10.1080/17590914.2024.2368382
Subash Sapkota, Sagor C Roy, Rami Shrestha, Karen P Briski
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引用次数: 0

摘要

下丘脑背内侧核(VMN)生长激素释放激素(Ghrh)的神经传递影响着激素的反调节分泌。背内侧 VMN Ghrh 神经元表达对代谢敏感的转录因子类固醇生成因子-1/NR5A1(SF-1)。本文使用体内 SF-1 基因敲除工具来研究雄性大鼠体内 SF-1 可能调节这些神经元中 Ghrh、协同递质生物合成酶和雌激素受体(ER)基因表达的基础和/或低血糖模式。单细胞多重 qPCR 分析表明,SF-1 可调节编码 Ghrh 的 mRNA 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蛋白标记的基础图谱。SF-1 siRNA预处理分别加剧或减弱了低血糖对谷氨酸脱羧酶67(GAD67/GAD1)和-65(GAD65/GAD2)转录本的抑制作用。低血糖会增加或减少一氧化氮合酶和谷氨酰胺酶 mRNA,SF-1 基因沉默可减轻这些反应。Ghrh和Ghrh受体转录物相应地不受低血糖影响或因低血糖而增加,但SF-1基因敲除会减少这两种基因的转录。低血糖对 ER-α 和 G 蛋白偶联-ER 基因表达的抑制在 SF-1 siRNA 预处理后被放大,而 ER-beta mRNA 则被放大。敲除 SF-1 会降低(皮质酮)或升高(胰高血糖素、生长激素(GH))基础反调节激素谱,但会放大低血糖性高皮质酮血症和-胰高血糖素血症或阻止升高的 GH 释放。结果证明了 SF-1 对 VMN Ghrh 神经元反调节神经递质和 ER 基因转录的控制。SF-1 可能调节 Ghrh 神经细胞对雌二醇的接受能力,并在葡萄糖平衡和系统失衡时释放独特的神经化学物质。雄性大鼠的 VMN Ghrh 神经元可能是 SF-1 控制葡萄糖反调节的底物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Steroidogenic Factor-1 Regulation of Dorsomedial Ventromedial Hypothalamic Nucleus Ghrh Neuron Transmitter Marker and Estrogen Receptor Gene Expression in Male Rat.

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.

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来源期刊
ASN NEURO
ASN NEURO NEUROSCIENCES-
CiteScore
7.70
自引率
4.30%
发文量
35
审稿时长
>12 weeks
期刊介绍: ASN NEURO is an open access, peer-reviewed journal uniquely positioned to provide investigators with the most recent advances across the breadth of the cellular and molecular neurosciences. The official journal of the American Society for Neurochemistry, ASN NEURO is dedicated to the promotion, support, and facilitation of communication among cellular and molecular neuroscientists of all specializations.
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