Expression of 11-Hydroxysteroid Dehydrogenase Type 1 in the Human Hypothalamus
Expression of 11-Hydroxysteroid Dehydrogenase Type 1 in the Human Hypothalamus
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DOI：
10.1111/jne.12017
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发表时间：
2013-05-01
影响因子：
3.2
通讯作者：
Fliers, E.
中科院分区：
文献类型：
--
作者：
Bisschop, P. H.;Dekker, M. J. H. J.;Fliers, E.
下丘脑是糖皮质激素的主要靶点，也是下丘脑-垂体-肾上腺（HPA）轴调节的关键结构。酶11羟类固醇脱氢酶1型（11 HSD 1）通过将生物学上无活性的可的松转化为其活性形式的皮质醇，在前受体水平调节各种组织中的糖皮质激素信号传导。本研究旨在评估11 HSD 1在人下丘脑中的表达。我们研究了11 HSD 1的表达在5个冷冻和4福尔马林固定，石蜡包埋的人下丘脑（从荷兰脑库获得）的聚合酶链反应和免疫细胞化学，分别。11 HSD 1 mRNA在视交叉上核（脑的生物钟）、视上核和室旁核（PVN）和漏斗核（啮齿动物弓状核的人类同源物）的区域中表达。免疫细胞化学法检测到11 HSD 1在同一细胞核内表达。在PVN，神经元11 HSD 1免疫反应共定位与促肾上腺皮质激素释放激素（CRH），精氨酸加压素和催产素，如所示的双重荧光染色。我们的数据表明，11 HSD 1广泛表达于人类下丘脑。其与CRH在PVN的共定位表明在HPA轴的糖皮质激素反馈的调制中的作用，而11 HSD 1在另外的和功能多样的下丘脑核中的表达指出了该酶在代谢、食欲和昼夜节律的调节中的作用。
The hypothalamus is a major target for glucocorticoids and a key structure for hypothalamic-pituitary-adrenal (HPA) axis setpoint regulation. The enzyme 11 hydroxysteroid dehydrogenase type 1 (11HSD1) modulates glucocorticoid signalling in various tissues at the prereceptor level by converting biologically inactive cortisone to its active form cortisol. The present study aimed to assess 11HSD1 expression in the human hypothalamus. We studied 11HSD1 expression in five frozen and four formalin-fixed, paraffin-embedded human hypothalami (obtained from the Netherlands Brain Bank) by the polymerase chain reaction and immunocytochemistry, respectively. 11HSD1 mRNA was expressed in the area of the suprachiasmatic nucleus, which is the biological clock of the brain, in the supraoptic nucleus and paraventricular nucleus (PVN), and in the infundibular nucleus, which is the human homologue of the rodent arcuate nucleus. 11HSD1 was detected by immunocytochemistry in the same nuclei. In the PVN, neuronal 11HSD1 immunoreactivity colocalised with corticotrophin-releasing hormone (CRH), arginine vasopressin and oxytocin, as shown by dual fluorescence staining. Our data demonstrate that 11HSD1 is widely expressed in the human hypothalamus. Its colocalisation with CRH in the PVN suggests a role in modulation of glucocorticoid feedback of the HPA axis, whereas the expression of 11HSD1 in additional and functionally diverse hypothalamic nuclei points to a role for the enzyme in the regulation of metabolism, appetite and circadian rhythms.