Institute for Society and Genetics, University of California Los Angeles, 621 Charles E Young Drive S, Los Angeles, CA 90095, USA; Laboratory of Neuroendocrinology, Brain Research Institute UCLA, Box 951761, University of California Los Angeles, Los Angeles, CA 90095, USA.
Laboratory of Neuroendocrinology, Brain Research Institute UCLA, Box 951761, University of California Los Angeles, Los Angeles, CA 90095, USA; Department of Integrative Biology and Physiology, University of California Los Angeles, 610 Charles E Young Drive E, Los Angeles, CA 90095, USA; Department of Ecology and Evolutionary Biology, University of California Los Angeles, 621 Charles E Young Drive S, Los Angeles, CA 90095, USA.
Gen Comp Endocrinol. 2021 May 1;305:113734. doi: 10.1016/j.ygcen.2021.113734. Epub 2021 Feb 4.
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 60 min 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.
糖皮质激素（GCs）的调节是多方面且动态的，它们是休息和应激时生理和行为的重要介质。11β 羟类固醇脱氢酶 11β-HSD1 和 11β-HSD2 分别催化 GCs 的再生和失活，为哺乳动物中 GCs 作用提供外周和中枢控制。虽然这些酶最近才在两种鸣禽中进行了研究，但中枢表达模式表明它们在鸟类和哺乳动物中的功能可能不同，并且对于外周表达如何调节循环 GCs 知之甚少。在这项研究中，我们利用 11β-HSD 抑制剂 carbenoxolone（CBX）来研究 11β-HSD 活性对循环 GCs 和成年斑胸草雀（Taeniopygia guttata）中枢 GC 依赖性基因表达的功能影响。外周注射 CBX 后 60 分钟，基础 GCs 明显增加，提示 11β-HSD2 在调节循环 GCs 中起主导作用。在成年斑胸草雀大脑中，虽然表达 11β-HSD2 但不表达 11β-HSD1，将微切割的脑区与 CBX 和应激水平的 GCs 共孵育对几种 GC 依赖性基因的表达没有影响。这些结果表明，外周 11β-HSD2 减弱了循环 GCs，而中枢 11β-HSD2 对基因表达几乎没有影响。相反，局部 GC 水平的快速 11β-HSD2 调节可能微调了大脑中的膜 GC 作用。这些结果为这一重要模型生物中 GC 分泌和作用的动态提供了新的见解。
