Luo X, Kiss A, Makara G, Lolait S J, Aguilera G
Section on Endocrine Physiology, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892.
J Neuroendocrinol. 1994 Dec;6(6):689-96. doi: 10.1111/j.1365-2826.1994.tb00636.x.
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 35S-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.(ABSTRACT TRUNCATED AT 250 WORDS)
促肾上腺皮质激素释放激素(CRH)是垂体促肾上腺皮质激素分泌的主要调节因子,在大脑中也作为一种神经递质发挥作用。为了确定CRH在应激过程中是否参与下丘脑功能的调节,研究了经历不同应激模式的大鼠下丘脑的CRH受体结合情况和CRH受体mRNA水平:束缚应激,一种身心应激模型;禁水和摄入2%盐水,渗透应激模型;腹腔注射高渗盐水,一种身心与渗透相结合的应激模型。与CRH受体在大脑中的结合分布一致,使用35S标记的cRNA探针进行的原位杂交研究显示,下丘脑前部区域的CRH受体mRNA水平较低,在急性或慢性暴露于任何一种所用应激模式后均未受影响。在基础条件下,视上核(SON)或室旁核(PVN)中没有CRH结合或CRH受体mRNA。然而,急性束缚应激开始2小时后,PVN小细胞部出现明显的CRH受体mRNA杂交信号,水平在2至4小时大幅增加,8小时下降,24小时消失。重复束缚应激后,PVN小细胞部发现相同的CRH受体mRNA杂交模式;水平与单次束缚应激2小时后8小时间隔重复24小时(3次)后的水平相似,在每天2小时束缚应激8天或14天后24小时,水平非常低,但仍可清晰检测到。另一方面,24或60小时的禁水以及12天摄入2%氯化钠诱导了SON和PVN大细胞部CRH受体mRNA的表达,但PVN小细胞部未出现。(摘要截短于250字)