Urocortin 1, urocortin 3/stresscopin, and corticotropin releasing factor receptors in human adrenal and its disorders
Urocortin 1, urocortin 3/stresscopin, and corticotropin releasing factor receptors in human adrenal and its disorders
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DOI：
10.1210/jc.2005-0090
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发表时间：
2005-08-01
影响因子：
5.8
通讯作者：
Sasano, H
中科院分区：
文献类型：
--
作者：
Fukuda, T;Takahashi, K;Sasano, H
尿皮质素1（Ucn 1）和尿皮质素3（Ucn 3）/应激蛋白是促肾上腺皮质激素释放因子（CRF）神经肽家族的新成员。Ucn 1结合CRF 1型（CRF 1）和2型受体（CRF 2），而Ucn 3是CRF 2的特异性激动剂。最近，直接参与本地合成的CRF家族在肾上腺皮质functions.Objective，设计和设置：我们研究了原位表达的UCN和CRF受体在非病理人类肾上腺及其疾病使用免疫组织化学和mRNA原位杂交。结果：UCN免疫反应位于皮质和髓质的非病理肾上腺。Ucn 1免疫反应性标记在髓质，而Ucn 3免疫染色主要在皮质。CRF 1型和CRF 2型均在皮质中表达，特别是在束状带和网状带中，但在髓质中非常弱或不可检测。免疫组化显示，Ucn 3和CRF 2共定位于85%以上的肾上腺皮质细胞。mRNA原位杂交证实了上述结果。在胎儿肾上腺中，UCN和CRF受体在皮质的胎儿区和确定区都有表达。Ucn和CRF受体在肾上腺嗜铬细胞瘤、肾上腺皮质腺瘤和癌中均有表达，但其阳性率低于正常肾上腺，提示Ucn 1、Ucn 3和CRF受体在肾上腺肿瘤中表达下调。Ucn 1、Ucn 3和CRF受体均表达于肾上腺皮质和髓质，可能在肾上腺生理功能中发挥重要作用。
Context: Urocortin 1 (Ucn1) and urocortin 3 (Ucn3)/stresscopin are new members of the corticotropin-releasing factor (CRF) neuropeptide family. Ucn1 binds to both CRF type 1 (CRF1) and type 2 receptors (CRF2), whereas Ucn3 is a specific agonist for CRF2. Recently, direct involvement of the locally synthesized CRF family in adrenocortical function has been proposed.Objective, Design, and Setting: We examined in situ expression of Ucn and CRF receptors in nonpathological human adrenal gland and its disorders using immunohistochemistry and mRNA in situ hybridization.Results: Ucn immunoreactivity was localized in the cortex and medulla of nonpathological adrenal glands. Ucn1 immunoreactivity was marked in the medulla, whereas Ucn3 was immunostained mostly in the cortex. Both CRF type 1 and CRF2 were expressed in the cortex, particularly in the zonae fasciculata and reticularis but very weakly or undetectably in the medulla. Immunohistochemistry in serial tissue sections with mirror images revealed that both Ucn3 and CRF2 were colocalized in more than 85% of the adrenocortical cells. mRNA in situ hybridization confirmed these findings above. In fetal adrenals, Ucn and CRF receptors were expressed in both fetal and definitive zones of the cortex. Ucn and CRF receptors were all expressed in the tumor cells of pheochromocytomas, adrenocortical adenomas, and carcinomas, but its positivity was less than that in nonpathological adrenal glands, suggesting that Ucn1, Ucn3, and CRF receptors were down-regulated in these adrenal neoplasms.Conclusions: Ucn1, Ucn3, and CRF receptors are all expressed in human adrenal cortex and medulla and may play important roles in physiological adrenal functions.