Aguilera G, Lightman S L, Kiss A
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Endocrinology. 1993 Jan;132(1):241-8. doi: 10.1210/endo.132.1.8380375.
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 micrograms, i.v.) 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 micrograms/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.
通过分析水剥夺48小时大鼠的下丘脑 - 肾上腺轴功能，研究了大细胞血管加压素能系统对促肾上腺皮质激素（ACTH）分泌调节的作用。水剥夺导致血浆渗透压和血管加压素（VP）水平显著升高，大细胞神经元中下丘脑VP mRNA和免疫反应性（ir）VP增加。虽然室旁核中促肾上腺皮质激素释放激素（CRH）mRNA水平降低，但秋水仙碱处理后室旁核神经元中irCRH积累正常或增加。同样，对照大鼠和水剥夺大鼠正中隆起中的irCRH含量及其在应激下的释放相似。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，静脉注射CRH（10微克）或15分钟固定应激刺激后的水平分别降低了47%（P<0.01）和43%（P<0.05）。在水剥夺期间注射CRH（7.5微克/天，皮下注射）并不能阻止ACTH反应降低。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固定应激的ACTH反应同样减弱。尽管垂体前叶阿黑皮素原（POMC）mRNA水平相似，但水剥夺大鼠的垂体ACTH含量降低，提示POMC合成或加工存在转录后抑制。数据表明，大细胞VP系统的渗透激活伴随着促肾上腺皮质激素细胞反应性降低，这种效应不是由于糖皮质激素反馈增加或下丘脑CRH缺乏所致。这些发现提示，在慢性渗透刺激期间，大细胞血管加压素能系统在ACTH分泌调节中不发挥重要作用。
