REGULATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS DURING WATER-DEPRIVATION
REGULATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS DURING WATER-DEPRIVATION
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DOI：
10.1210/en.132.1.241
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发表时间：
1993-01-01
期刊：
影响因子：
4.8
通讯作者：
KISS, A
中科院分区：
文献类型：
--
作者：
AGUILERA, G;LIGHTMAN, SL;KISS, A
本文通过对禁水48 h大鼠下丘脑-肾上腺轴功能的分析，探讨了大细胞加压素能系统对ACTH分泌的调节作用。结果表明，水剥夺可导致大鼠血浆渗透压和加压素（VP）水平显著升高，下丘脑VP mRNA和大细胞神经元内VP免疫反应阳性（ir）也显著增加。虽然室旁核CRH mRNA水平降低，但秋水仙碱处理后室旁核神经元中irCRH积聚正常或增加。同样，irCRH含量在正中隆起和压力下释放的控制和水剥夺大鼠相似。虽然两组的基础血浆ACTH水平相似（34.5 ± 3.8和39.8 ± 3.3 pg/ml），但在限水大鼠中，CRH注射（10 μ g，iv）或15分钟制动应激刺激的水平分别降低了47%（P < 0.01）和43%（P < 0.05）。在禁水期间注射CRH（7.5 μ g/天，sc）不能预防ACTH反应的降低。与ACTH反应相反，基础和CRH刺激的血浆皮质酮水平显著升高（P < 0.001），对急性应激的反应正常。ACTH分泌的抑制不是由于糖皮质激素反馈增加，因为在接受皮质酮替代的肾上腺切除大鼠中观察到对急性制动应激的类似钝化ACTH反应。尽管垂体POMC mRNA的水平相似，垂体ACTH含量减少，在水剥夺大鼠，表明POMC合成或加工的转录后抑制。这些数据表明，大细胞VP系统的渗透激活伴随着减少的反应性的促肾上腺皮质激素，效果是不是由于增加糖皮质激素反馈或下丘脑CRH缺乏症。这些结果表明，大细胞加压素能系统不发挥重要作用，在慢性渗透刺激的ACTH分泌的调节。
The contribution of the magnocellular vasopressinergic system to the regulation of ACTH secretion was studied by analysis of hypothalamic-adrenal axis function in rats subjected to water deprivation for 48 h. Water deprivation resulted in marked increases in plasma osmolarity and vasopressin (VP) levels and hypothalamic VP mRNA and immunoreactive (ir) VP in magnocellular neurons. While CRH mRNA levels in the paraventricular nucleus were decreased, irCRH accumulation in paraventricular nucleus neurons after colchicine treatment was normal or increased. Similarly, the irCRH content in the median eminence and its release under stress were similar in control and water-deprived rats. While basal plasma ACTH levels were similar in both groups (34.5 +/- 3.8 and 39.8 +/- 3.3 pg/ml), levels stimulated by CRH injection (10 mug, iv) or 15-min immobilization stress were reduced by 47% (P < 0.01) and 43% (P < 0.05), respectively, in water-restricted rats. The decreased ACTH responses were not prevented by injection of CRH (7.5 mug/day, sc) during the period of water deprivation. In contrast to the ACTH responses, basal and CRH-stimulated plasma corticosterone levels were significantly elevated (P < 0.001), and the responses to acute stress were normal. The inhibition of ACTH secretion was not due to increased glucocorticoid feedback, since similar blunted ACTH responses to acute immobilization stress were observed in adrenalectomized rats receiving corticosterone replacement. Despite similar levels of pituitary POMC mRNA, pituitary ACTH content was reduced in water-deprived rats, suggesting a posttranscriptional inhibition of POMC synthesis or processing. The data demonstrate that osmotic activation of the magnocellular VP system is accompanied by reduced responsiveness of the corticotrophs, an effect that is not due to increased glucocorticoid feedback or hypothalamic CRH deficiency. These findings suggest that the magnocellular vasopressinergic system does not play an important role in the regulation of ACTH secretion during chronic osmotic stimulation.