Fukuda Tsuyoshi, Takahashi Kazuhiro, Suzuki Takashi, Saruta Masayuki, Watanabe Mika, Nakata Taisuke, Sasano Hironobu
Department of Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
J Clin Endocrinol Metab. 2005 Aug;90(8):4671-8. doi: 10.1210/jc.2005-0090. Epub 2005 May 24.
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.
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.
Ucn1, Ucn3, and CRF receptors are all expressed in human adrenal cortex and medulla and may play important roles in physiological adrenal functions.
尿皮质素1（Ucn1）和尿皮质素3（Ucn3）/应激肽是促肾上腺皮质激素释放因子（CRF）神经肽家族的新成员。Ucn1与CRF 1型（CRF1）和2型受体（CRF2）均结合，而Ucn3是CRF2的特异性激动剂。最近，有人提出局部合成的CRF家族直接参与肾上腺皮质功能。
目的、设计和研究地点：我们使用免疫组织化学和mRNA原位杂交技术，研究了Ucn和CRF受体在非病理性人肾上腺及其疾病中的原位表达。
Ucn免疫反应性定位于非病理性肾上腺的皮质和髓质。Ucn1免疫反应性在髓质中明显，而Ucn3主要在皮质中呈免疫染色。CRF1型和CRF2型受体均在皮质中表达，特别是在束状带和网状带，但在髓质中表达非常弱或无法检测到。连续组织切片的镜像免疫组织化学显示，Ucn3和CRF2在超过85%的肾上腺皮质细胞中共定位。mRNA原位杂交证实了上述发现。在胎儿肾上腺中，Ucn和CRF受体在皮质的胎儿区和永久区均有表达。Ucn和CRF受体在嗜铬细胞瘤、肾上腺皮质腺瘤和癌的肿瘤细胞中均有表达，但其阳性率低于非病理性肾上腺，提示Ucn1、Ucn3和CRF受体在这些肾上腺肿瘤中下调。
Ucn1、Ucn3和CRF受体均在人肾上腺皮质和髓质中表达，可能在肾上腺生理功能中发挥重要作用。
