Expression of α1b Adrenoceptor mRNA in Corticotropin-Releasing Hormone-Containing Cells of the Rat Hypothalamus and Its Regulation by Corticosterone
Expression of α1b Adrenoceptor mRNA in Corticotropin-Releasing Hormone-Containing Cells of the Rat Hypothalamus and Its Regulation by Corticosterone
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α1b肾上腺素受体mRNA在大鼠下丘脑促肾上腺皮质激素释放激素细胞中的表达及其对皮质酮的调节
作者：
H. Day;S. Campeau;S. Watson;H. Akil
相当多的证据支持脑干肾上腺素能和去甲肾上腺素能传入下丘脑室旁核(PVN)的促肾上腺皮质激素释放激素(CRH)细胞，在控制下丘脑-垂体-肾上腺皮质(HPA)轴功能中发挥作用。然而，关于PVN中含有CRH的细胞中特定的肾上腺素受体(ADR)亚型知之甚少。在这里，我们用双杂交技术证明了编码CRH1b阿片受体的基因与α共存于大鼠的下丘脑室旁核。此外，我们证实这些含有α1b ADR mRNA的细胞在束缚、游泳或免疫应激后与c-FOS mRNA共定位，是应激反应的细胞。为探讨循环糖皮质激素对α1b ADR mRNA表达的影响，雄性大鼠双侧肾上腺切除或假手术后1、3、7、14d处死动物，原位杂交结果显示，ADX后7d和14d，PVN中α1bADR基因表达增加，但在海马、杏仁核和中缝背侧未见改变。皮质酮替代组(10 mg或50 mg)或安慰剂治疗7d后，皮质酮替代组(10 Mg)可使阿霉素诱导的下丘脑室旁核α1bADR基因表达水平降低至对照组水平，而50 mg皮质酮替代组可使PVNα1bADR基因表达降低。此外，PVN患者血浆皮质酮水平与α1b ADR基因表达呈显著负相关。我们得出结论，α1b ADR基因在室旁核内含有CRH的应激反应细胞中表达，并且对循环皮质酮水平高度敏感。由于α1B肾上腺素受体的激活在脑内主要是兴奋性的，我们预测该受体在促进HPA轴反应中发挥重要作用。
Considerable evidence supports a role for brainstem adrenergic and noradrenergic inputs to corticotropin-releasing hormone (CRH) cells of the hypothalamic paraventricular nucleus (PVN), in the control of hypothalamic–pituitary–adrenocortical (HPA) axis function. However, little is known about specific adrenoceptor (ADR) subtypes in CRH-containing cells of the PVN. Here we demonstrate, using dualin situ hybridization, that mRNA encoding α1b ADR is colocalized with CRH in the rat PVN. Furthermore, we confirm that these α1b ADR mRNA-containing cells are stress-responsive, by colocalization with c-fos mRNA after restraint, swim, or immune stress. To determine whether expression of α1b ADR mRNA is influenced by circulating glucocorticoids, male rats underwent bilateral adrenalectomy (ADX) or sham surgery, and were killed after 1, 3, 7, or 14 d. In situ hybridization revealed levels of α1b ADR mRNA were increased in the PVN 7 and 14 d after ADX, but were not altered in the hippocampus, amygdala, or dorsal raphe. Additional rats underwent ADX or sham surgery and received a corticosterone pellet (10 or 50 mg) or placebo for 7 d. Corticosterone replacement (10 mg) reduced the ADX-induced increase in PVN α1b ADR mRNA to control levels, whereas 50 mg of corticosterone replacement resulted in a decrease in PVN α1b ADR mRNA as compared with all other groups. Furthermore, levels of plasma corticosterone were significantly correlated (inverse relationship) with α1b ADR mRNA in the PVN. We conclude that α1b ADR mRNA is expressed in CRH-containing, stress-responsive cells of the PVN and is highly sensitive to circulating levels of corticosterone. Because activation of the α1B adrenoceptor is predominantly excitatory within the brain, we predict that this receptor plays an important role in facilitation of the HPA axis response.
糖皮质激素诱导 DTT1 MF-2 平滑肌细胞中 α 1B 肾上腺素受体基因的转录和表达。
DOI：
10.1172/jci115315
发表时间：
1991
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Sakaue,M;Hoffman,BB
通讯作者：
Hoffman,BB
影响因子：
5.5
作者：
PAN, ZZ;GRUDT, TJ;WILLIAMS, JT
通讯作者：
WILLIAMS, JT
DOI：
10.1073/pnas.93.6.2359
发表时间：
1996-03-19
影响因子：
11.1
作者：
Li, HY;Ericsson, A;Sawchenko, PE
通讯作者：
Sawchenko, PE