Tanimura S M, Watts A G
Neuroscience Program, The Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-2520, USA.
J Neuroendocrinol. 2000 Aug;12(8):715-22. doi: 10.1046/j.1365-2826.2000.00504.x.
We have used in situ hybridization and radio-immunoassay to compare temporal dynamics of components in the hypothalamo-pituitary limb of the hypothalamo-pituitary-adrenal axis during sustained hypovolemic stress in adrenalectomized (ADX) rats to those previously reported in intact animals. We asked three questions: first, does corticotropin-releasing hormone (CRH) gene transcription occur in neuroendocrine neurones of the hypothalamic paraventricular nucleus (PVH) of ADX rats, and if so, how is it temporally organized; second, what is the expression pattern of the vasopressin and other genes known to be colocalized in these neuroendocrine neurones; third, if adrenocorticotropin hormone (ACTH) secretion occurs, what is its temporal profile? We found that sustained hypovolemia evoked a brief episode of CRH gene transcription in ADX rats that occurred earlier than in intact rats. However, in contrast to saline-injected controls, this activation was not maintained because declines in CRH hnRNA and mRNA were seen as the stress continued. Although increased vasopressin gene transcription was not seen in intact hypovolemic rats, robust increases were measured throughout in ADX rats, suggesting that in the absence of corticosterone the vasopressin gene is transcribed preferentially to the CRH gene during sustained hypovolemia. c-fos and preproenkephalin mRNA profiles also exhibited earlier onsets compared to intact rats. Finally, the onset and duration of ACTH secretion was the same in ADX rats as previously reported in intact rats. Collectively, these data support two hypotheses regarding the actions of corticosterone. First, that it provides some form of facilitatory signal allowing neuroendocrine CRH transcriptional mechanisms to remain active during sustained hypovolemia. Second, that it strongly inhibits the response of the vasopressin gene to hypovolemic stress.
我们运用原位杂交和放射免疫分析法，比较了肾上腺切除（ADX）大鼠在持续性低血容量应激期间，下丘脑-垂体-肾上腺轴的下丘脑-垂体分支中各成分的时间动态变化，以及之前在完整动物中报道的情况。我们提出了三个问题：第一，促肾上腺皮质激素释放激素（CRH）基因转录是否发生在ADX大鼠下丘脑室旁核（PVH）的神经内分泌神经元中？如果发生，其时间组织方式是怎样的？第二，已知与这些神经内分泌神经元共定位的血管加压素和其他基因的表达模式是怎样的？第三，如果促肾上腺皮质激素（ACTH）分泌发生，其时间特征是怎样的？我们发现，持续性低血容量在ADX大鼠中诱发了一段短暂的CRH基因转录，其发生时间早于完整大鼠。然而，与注射生理盐水的对照组不同，这种激活并未持续，因为随着应激的持续，CRH核不均一RNA（hnRNA）和信使核糖核酸（mRNA）水平下降。虽然在完整的低血容量大鼠中未观察到血管加压素基因转录增加，但在整个实验过程中，ADX大鼠的血管加压素基因转录显著增加，这表明在缺乏皮质酮的情况下，持续性低血容量期间血管加压素基因比CRH基因更优先转录。与完整大鼠相比，原癌基因c-fos和前脑啡肽原mRNA水平的变化也出现得更早。最后，ADX大鼠中ACTH分泌的起始和持续时间与之前在完整大鼠中报道的相同。总体而言，这些数据支持了关于皮质酮作用的两个假说。第一，它提供了某种形式的促进信号，使神经内分泌CRH转录机制在持续性低血容量期间保持活跃。第二，它强烈抑制血管加压素基因对低血容量应激的反应。
