11ß hydroxysteroid dehydrogenases regulate circulating glucocorticoids but not central gene expression.
11ß hydroxysteroid dehydrogenases regulate circulating glucocorticoids but not central gene expression.
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DOI：
10.1016/j.ygcen.2021.113734
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发表时间：
2021-05-01
影响因子：
2.7
通讯作者：
Schlinger BA
中科院分区：
文献类型：
--
作者：
Rensel MA;Schlinger BA
糖皮质激素（GCs），在休息和应激期间的生理和行为的重要介质，调节是多方面的和动态的。11 β羟基类固醇脱氢酶11 β-HSD 1和11 β-HSD 2分别催化GC的再生和失活，并在哺乳动物中提供对GC作用的外周和中枢控制。虽然这些酶最近才在两种鸣禽物种中进行了研究，但中心表达模式表明它们在鸟类和哺乳动物中的功能可能不同，而且人们对外周表达如何调节循环GC知之甚少。在这项研究中，我们利用11-HSD抑制剂甘珀酸（CBX）探测11-HSD活性对成年斑胸草雀（Taeniopygia guttata）循环GC和中枢GC依赖性基因表达的功能影响。外周CBX注射在注射后60分钟产生基线GC的显著增加，表明11 β-HSD 2在调节循环GC中的主导作用。在成年斑胸草雀的大脑中，11 β-HSD 2而不是11 β-HSD 1表达，与CBX和应激水平GC共孵育的显微解剖的大脑区域对几个GC依赖性基因的表达没有影响。这些结果表明，外周11 β-HSD 2减弱循环GC，而中枢11 β-HSD 2对基因表达几乎没有影响。相反，基于11 β-HSD 2的局部GC水平的快速调节可能会微调大脑中的膜GC作用。这些结果提供了新的见解GC分泌和行动的动态在这个重要的模式生物。
Regulation of glucocorticoids (GCs), important mediators of physiology and behavior at rest and during stress, is multi-faceted and dynamic. The 11ß hydroxysteroid dehydrogenases 11ß-HSD1 and 11ß-HSD2 catalyze the regeneration and inactivation of GCs, respectively, and provide peripheral and central control over GC actions in mammals. While these enzymes have only recently been investigated in just two songbird species, central expression patterns suggest that they may function differently in birds and mammals, and little is known about how peripheral expression regulates circulating GCs. In this study, we utilized the 11ß-HSD inhibitor carbenoxolone (CBX) to probe the functional effects of 11ß-HSD activity on circulating GCs and central GC-dependent gene expression in the adult zebra finch (Taeniopygia guttata). Peripheral CBX injection produced a marked increase in baseline GCs 60min after injection, suggestive of a dominant role for 11ß-HSD2 in regulating circulating GCs. In the adult zebra finch brain, where 11ß-HSD2 but not 11ß-HSD1 is expressed, co-incubation of micro-dissected brain regions with CBX and stress-level GCs had no impact on expression of several GC-dependent genes. These results suggest that peripheral 11ß-HSD2 attenuates circulating GCs, whereas central 11ß-HSD2 has little impact on gene expression. Instead, rapid 11ß-HSD2-based regulation of local GC levels might fine-tune membrane GC actions in brain. These results provide new insights into the dynamics of GC secretion and action in this important model organism.
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