STRESS-SPECIFIC REGULATION OF CORTICOTROPIN-RELEASING HORMONE-RECEPTOR EXPRESSION IN THE PARAVENTRICULAR AND SUPRAOPTIC NUCLEI OF THE HYPOTHALAMUS IN THE RAT
STRESS-SPECIFIC REGULATION OF CORTICOTROPIN-RELEASING HORMONE-RECEPTOR EXPRESSION IN THE PARAVENTRICULAR AND SUPRAOPTIC NUCLEI OF THE HYPOTHALAMUS IN THE RAT
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DOI：
10.1111/j.1365-2826.1994.tb00636.x
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发表时间：
1994-12-01
影响因子：
3.2
通讯作者：
AGUILERA, G
中科院分区：
文献类型：
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作者：
LUO, X;KISS, A;AGUILERA, G
促肾上腺皮质激素释放激素（CRH）是垂体ACTH分泌的主要调节因子，也是大脑中的一种神经递质。为了确定CRH是否参与应激时下丘脑功能的调节，我们研究了不同应激模式下大鼠下丘脑CRH受体结合和CRH受体mRNA水平：生理-心理模型固定；水剥夺和2%生理盐水摄入，渗透模型；高渗生理盐水注射，生理-心理和渗透相结合的模型。与CRH受体在大脑中的结合分布一致，使用s -35标记的cRNA探针的原位杂交研究显示，下丘脑前区CRH受体mRNA水平低，在急性或慢性暴露于任何应激模式下均不受影响。在基础条件下，视上核（SON）和室旁核（PVN）中没有CRH结合或CRH受体mRNA。然而，在急性固定开始2 h后，在PVN的细胞小分裂中出现了明显的CRH受体mRNA杂交，在2 - 4 h时水平显著增加，在8 h时下降，在24 h时消失，重复固定后PVN细胞小分裂中CRH受体mRNA的杂交模式相同；CRH受体mRNA的表达水平与连续固定24小时（3次），每隔8小时固定一次后2小时的应激水平相似，并且在每天固定2小时后8天或14天的24小时非常低，但可以清楚地检测到。另一方面，24或60小时的缺水和12天摄入2% NaCl诱导了PVN的SON和大细胞PVN中CRH受体mRNA的表达，但在PVN的小细胞部分没有表达。高渗生理盐水单次（4小时后）或每隔8小时重复注射24小时（3次注射），或每天注射一次，连续8或14天，下丘脑小细胞区和大细胞区均显示CRH受体mRNA。与CRH受体mRNA的表达一致，放射自显像研究显示，固定后PVN的细胞内分裂中结合了i -125- tyrr - ocrh；渗透刺激后PVN的大细胞分裂，以及i.p.高渗盐水注射后PVN和SON的变化。这些数据表明，小细胞和大细胞系统的应激特异性激活与CRH受体的表达有关，并表明CRH在下丘脑功能的自动调节中起作用。
Corticotropin releasing hormone (CRH), a major regulator of pituitary ACTH secretion, also acts as a neurotransmitter in the brain. To determine whether CRH is involved in the regulation of hypothalamic function during stress, CRH receptor binding and CRH receptor mRNA levels were studied in the hypothalamus of rats subjected to different stress paradigms: immobilization, a physical-psychological model; water deprivation and 2% saline intake, osmotic models; and i.p. hypertonic saline injection, a combined physical-psychological and osmotic model. In agreement with the distribution of CRH receptor binding in the brain, in situ hybridization studies using S-35-labeled cRNA probes revealed low levels of CRH receptor mRNA in the anterior hypothalamic area, which were unaffected after acute or chronic exposure to any of the stress paradigms used. Under basal conditions, there was no CRH binding or CRH receptor mRNA in the supraoptic (SON) or paraventricular (PVN) nuclei. However, 2 h after the initiation of acute immobilization, CRH receptor mRNA hybridization became evident in the parvicellular division of the PVN, with levels substantially increasing from 2 to 4 h, decreasing at 8 h and disappearing by 24 h. identical hybridization patterns of CRH receptor mRNA were found in the parvicellular PVN after repeated immobilization; levels were similar to those after 2 h single stress following immobilization at 8-hourly intervals for 24 h (3 times), and very low, but clearly detectable 24 h after 8 or 14 days daily immobilization for 2 h. On the other hand, water deprivation for 24 or 60 h and intake of 2% NaCl for 12 days induced expression of CRH receptor mRNA in the SON and magnocellular PVN, but not in the parvicellular pars of the PVN. Both parvicellular and magnocellular hypothalamic areas showed CRH receptor mRNA following i.p. hypertonic saline injection, single (4 h after) or repeated at 8-hourly intervals for 24 h (3 injections), or one injection daily for 8 or 14 days. Consistent with the expression of CRH receptor mRNA, autoradiographic studies showed binding of I-125-Tyr-oCRH in the parvicellular division of the PVN after immobilization; in the magnocellular division of the PVN after osmotic stimulation, and in the PVN and SON after i.p. hypertonic saline injection. The data show that stress-specific activation of the parvicellular and magnocellular systems is associated with CRH receptor expression, and suggest a role for CRH in the autoregulation of hypothalamic function.