Cellular and extracellular regulatory mechanisms for hypothalamic 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。

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.