Herman J P
Department of Anatomy and Neurobiology, University of Kentucky School of Medicine, Lexington 40536-0084, USA.
J Comp Neurol. 1995 Dec 4;363(1):15-27. doi: 10.1002/cne.903630103.
Hypothalamic arginine vasopressin-containing neurons are prime elements in central circuits regulating the hypothalamo-pituitary-adrenocortical stress response. It is known that release and synthesis of vasopressin are cued by stressful stimuli. The present study was designed to assess effects of stress on vasopressin transcription and mRNA expression in defined populations of vasopressin neurons in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Intron- and exon-directed in situ hybridization analyses were used to examine stress regulation of vasopressin heteronuclear (hn) gene transcription and mRNA levels. Actions of glucocorticoids on vasopressin induction were tested using adrenalectomized rats implanted with subcutaneous pellets delivering a constant, physiological dose of corticosterone. Pellet implantation into adrenalectomized rats allows for normal pituitary-adrenal tone in the absence of the ability to mount glucocorticoid stress responses. Elevation of vasopressin heteronuclear (hn) RNA in the medial parvicellular PVN was observed in both normal and adrenalectomized-corticosterone replaced rats as early as 30 minutes after stress initiation. In control rats, vasopressin hnRNA levels returned to baseline by 120 minutes. In contrast, vasopressin hnRNA remained elevated 120 minutes post-restraint in adrenalectomized-corticosterone replaced rats, indicating that the glucocorticoid stress response acts to rapidly inhibit vasopressin transcription. Significant changes in post-stress vasopressin mRNA levels were observed in the parvicellular PVN of control rats 90 minutes following restraint induction, returning to normal expression profiles by 120 minutes. Adrenalectomized-replaced rats showed elevated vasopressin mRNA expression at all time points examined. No changes were observed in magnocellular vasopressin-containing nuclei at any time point, suggesting that magnocellular vasopressin is not induced by this particular stress paradigm. Thus, in parvicellular paraventricular nucleus neurons the vasopressin gene is rapidly induced by stress. Restraint-induced up-regulation of vasopressin transcription is limited by glucocorticoid secretion, consistent with direct actions of glucocorticoid negative feedback on the vasopressin gene in parvicellular neurons.
下丘脑含精氨酸加压素的神经元是调节下丘脑 - 垂体 - 肾上腺皮质应激反应的中枢回路中的主要成分。已知加压素的释放和合成受应激刺激的提示。本研究旨在评估应激对下丘脑室旁核（PVN）和视上核（SON）中特定群体的加压素神经元中加压素转录和mRNA表达的影响。采用内含子和外显子定向原位杂交分析来检测加压素异核（hn）基因转录和mRNA水平的应激调节。使用植入皮下丸剂以递送恒定生理剂量皮质酮的肾上腺切除大鼠来测试糖皮质激素对加压素诱导的作用。将丸剂植入肾上腺切除大鼠可在缺乏产生糖皮质激素应激反应能力的情况下维持正常的垂体 - 肾上腺张力。早在应激开始后30分钟，在正常大鼠和肾上腺切除 - 皮质酮替代大鼠的内侧小细胞PVN中均观察到加压素异核（hn）RNA升高。在对照大鼠中，加压素hnRNA水平在120分钟时恢复到基线。相比之下，在肾上腺切除 - 皮质酮替代大鼠中，束缚后120分钟加压素hnRNA仍保持升高，表明糖皮质激素应激反应起到快速抑制加压素转录的作用。在对照大鼠束缚诱导后90分钟，在小细胞PVN中观察到应激后加压素mRNA水平有显著变化，在120分钟时恢复到正常表达水平。肾上腺切除替代大鼠在所有检测时间点均显示加压素mRNA表达升高。在任何时间点，含大细胞加压素的核均未观察到变化，表明大细胞加压素不会被这种特定的应激模式诱导。因此，在小细胞室旁核神经元中，加压素基因可被应激快速诱导。束缚诱导的加压素转录上调受糖皮质激素分泌的限制，这与糖皮质激素对小细胞神经元中加压素基因的直接负反馈作用一致。
