Corticotropin-releasing factor (CRF) and the urocortins differentially regulate catecholamine secretion in human and rat adrenals, in a CRF receptor type-specific manner
Corticotropin-releasing factor (CRF) and the urocortins differentially regulate catecholamine secretion in human and rat adrenals, in a CRF receptor type-specific manner
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DOI：
10.1210/en.2006-0967
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发表时间：
2007-04-01
期刊：
影响因子：
4.8
通讯作者：
Margioris, A. N.
中科院分区：
文献类型：
--
作者：
Dermitzaki, E.;Tsatsanis, C.;Margioris, A. N.
促肾上腺皮质激素释放因子(CRF)影响中枢和外周的儿茶酚胺的产生。本工作的目的是研究CRF及其相关多肽及其受体在人和大鼠肾上腺髓质中的存在及其对儿茶酚胺合成和分泌的直接影响。用免疫细胞化学、免疫荧光和RT-PCR方法检测CRF、UCN1、UCN2和CRF受体1、2在人和大鼠肾上腺髓质以及PC12嗜铬细胞瘤细胞的表达。分散的人和大鼠肾上腺嗜铬细胞暴露于CRF1受体激动剂后，以剂量依赖的方式诱导儿茶酚胺的分泌，这种作用在30min时达到高峰，而CRF2受体激动剂则抑制儿茶酚胺的分泌。CRF1和CRF2拮抗剂分别阻断这两种作用。CRF多肽通过改变浆膜下肌动蛋白微丝聚合来影响儿茶酚胺的分泌。CRF多肽也影响儿茶酚胺的合成。在大鼠嗜铬细胞和PC12细胞中，CRF1和CRF2激动剂通过酪氨酸羟化酶诱导儿茶酚胺的合成。然而，在人嗜铬细胞中，CRF1受体的激活诱导了酪氨酸羟化酶，而CRF2的激活则抑制了它。总之，在人和大鼠肾上腺中似乎都存在一个复杂的肾上腺内CRF-UCN/CRF-受体系统，控制儿茶酚胺的分泌和合成。
Corticotropin-releasing factor (CRF) affects catecholamine production both centrally and peripherally. The aim of the present work was to examine the presence of CRF, its related peptides, and their receptors in the medulla of human and rat adrenals and their direct effect on catecholamine synthesis and secretion. CRF, urocortin I (UCN1), urocortin II (UCN2), and CRF receptor type 1 (CRF1) and 2 (CRF2) were present in human and rat adrenal medulla as well as the PC12 pheochromocytoma cells by immunocytochemistry, immunofluorescence, and RT-PCR. Exposure of dispersed human and rat adrenal chromaffin cells to CRF1 receptor agonists induced catecholamine secretion in a dose-dependent manner, an effect peaking at 30 min, whereas CRF2 receptor agonists suppressed catecholamine secretion. The respective effects were blocked by CRF1 and CRF2 antagonists. CRF peptides affected catecholamine secretion via changes of subplasmaliminal actin filament polymerization. CRF peptides also affected catecholamine synthesis. In rat chromaffin and PC12 cells, CRF1 and CRF2 agonists induced catecholamine synthesis via tyrosine hydroxylase. However, in human chromaffin cells, activation of CRF1 receptors induced tyrosine hydroxylase, whereas activation of CRF2 suppressed it. In conclusion, it appears that a complex intraadrenal CRF-UCN/CRF-receptor system exists in both human and rat adrenals controlling catecholamine secretion and synthesis.