Cellular and extracellular regulatory mechanisms for hypothalamic CRH gene expression

下丘脑CRH基因表达的细胞和细胞外调节机制

• 批准号: 10671029
• 负责人: ITOI Keiichi
• 金额: $ 2.05万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671029/
• 关键词: Hypothalamus; CRH; gene; in situ hybridization; rat; A kinase; C kinase; transcription; in situ ハイブリダイゼーション

The hypothalamic-pituitary-adrenal axis is necessary to maintain the internal milieu of living organisms. Norepinephrine (NE) has been shown to stimulate CRH gene expression in the paraventricular nucleus of the hypothalamus (PVN). On the other hand, CRH colocalizes with arginine vasopressin (AVP) in the parvocellular division of the PVN. We investigated the effect of NE on primary transcripts of CRH and AVP in the PVN by microinjection of NE directly into the PVN of conscious rats. NE stimulated CRH gene transcription, whereas it had no significant effect on AVP gene transcription. We reported the same experiments using rats, adrenalectomized and supplemented with low-dose corticosterone. It became clear that glucocorticoid affects CRH- and AVP gene in a different manner, AVP gene being more sensitive to the circulating glucocorticoid in this acute experimental paradigm. Furthermore, TPA stimulated CRH gene expression in a human neuroblastoma cell line, BE(2)-M17, suggesting the physiological role of the PKC pathway in the regulation of CRH gene expression.

下丘脑-垂体-肾上腺轴是维持生物体内环境所必需的。去甲肾上腺素（NE）已被证明刺激下丘脑室旁核（PVN）中CRH基因的表达。另一方面，CRH与精氨酸加压素（AVP）在PVN的小细胞分裂中共定位。本实验通过将NE直接微量注射到清醒大鼠的室旁核，观察了NE对室旁核CRH和AVP初级转录的影响。NE刺激CRH基因转录，而对AVP基因转录无明显影响。我们报告了相同的实验使用大鼠，肾上腺切除和补充低剂量皮质酮。很明显，糖皮质激素以不同的方式影响CRH-和AVP基因，AVP基因在这种急性实验范例中对循环糖皮质激素更敏感。此外，TPA刺激人神经母细胞瘤细胞系BE（2）-M17中CRH基因的表达，提示PKC途径在CRH基因表达调节中的生理作用。

项目成果

Sugawara A: "A case of inherited GH deficiency with a 6.7-K6 deletion of GH-1 gene"Clin.Pediat.Endouinol.. 7. 41-46 (1998)

菅原 A：“遗传性 GH 缺乏症伴 GH-1 基因 6.7-K6 缺失”Clin.Pediat.Endouinol.. 7. 41-46 (1998)

Keiichi Itoi: "Molecular mechanisms for the regulation of corticotropin-releasing hormone neurons in the hypothalamus"Mol. Neurobiology. (印刷中). (2000)

Keiichi Itoi：“调节下丘脑促肾上腺皮质激素释放激素神经元的分子机制”Mol Neurobiology（出版中）。

Sugawara A.: "A case of inherited GH deficiency with a 6.7-Kb deletion of GH-1 gene" Clin.Pediatr.Endocrinol.7. 41-46 (1998)

Sukawara A.：“一例 GH-1 基因 6.7-Kb 缺失的遗传性 GH 缺乏症”Clin.Pediatr.Endocrinol.7。

Lopez-Figueroa MO: "Regulation of nitric oxide synthase messenger RNA in the rat hippocampus by glucocorticoids"Neuroscience. 87. 439-446 (1998)

Lopez-Figueroa MO：“糖皮质激素对大鼠海马一氧化氮合酶信使 RNA 的调节”神经科学。

Keiichi Itoi: "Cellular and extracellular regulatory mechanisms of hypothelamic CRH neurons" Endocrine J.45. 13-33 (1998)

Keiichi Itoi：“下丘脑 CRH 神经元的细胞和细胞外调节机制”内分泌 J.45。