Rensel Michelle A, Ding Jessica A, Pradhan Devaleena S, Schlinger Barney A
The Institute for Society and Genetics, University of California, Los Angeles, Los Angeles, CA, United States.
Laboratory of Neuroendocrinology, University of California, Los Angeles, Los Angeles, CA, United States.
Front Endocrinol (Lausanne). 2018 Mar 12;9:86. doi: 10.3389/fendo.2018.00086. eCollection 2018.
Glucocorticoid (GC) hormones act on the brain to regulate diverse functions, from behavior and homeostasis to the activity of the hypothalamic-pituitary-adrenal axis. Local regeneration and metabolism of GCs can occur in target tissues through the actions of the 11β-hydroxysteroid dehydrogenases [11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and 11 beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2), respectively] to regulate access to GC receptors. Songbirds have become especially important model organisms for studies of stress hormone action; however, there has been little focus on neural GC metabolism. Therefore, we tested the hypothesis that 11β-HSD1 and 11β-HSD2 are expressed in GC-sensitive regions of the songbird brain. Localization of 11β-HSD expression in these regions could provide precise temporal and spatial control over GC actions. We quantified GC sensitivity in zebra finch () brain by measuring glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) expression across six regions, followed by quantification of 11β-HSD1 and 11β-HSD2 expression. We detected GR, MR, and 11β-HSD2 mRNA expression throughout the adult brain. Whereas 11β-HSD1 expression was undetectable in the adult brain, we detected low levels of expression in the brain of developing finches. Across several adult brain regions, expression of 11β-HSD2 covaried with GR and MR, with the exception of the cerebellum and hippocampus. It is possible that receptors in these latter two regions require direct access to systemic GC levels. Overall, these results suggest that 11β-HSD2 expression protects the adult songbird brain by rapid metabolism of GCs in a context and region-specific manner.
糖皮质激素(GC)作用于大脑,调节从行为、内环境稳定到下丘脑 - 垂体 - 肾上腺轴活性等多种功能。通过11β - 羟基类固醇脱氢酶(分别为1型11β - 羟基类固醇脱氢酶(11β - HSD1)和2型11β - 羟基类固醇脱氢酶(11β - HSD2))的作用,GC在靶组织中可发生局部再生和代谢,以调节对GC受体的作用。鸣禽已成为研究应激激素作用的特别重要的模式生物;然而,对神经GC代谢的关注很少。因此,我们检验了这样一个假设,即11β - HSD1和11β - HSD2在鸣禽大脑的GC敏感区域表达。这些区域中11β - HSD表达的定位可为GC作用提供精确的时空控制。我们通过测量六个区域的糖皮质激素受体(GR)和盐皮质激素受体(MR)表达来量化斑胸草雀大脑中的GC敏感性,随后对11β - HSD1和11β - HSD2表达进行量化。我们在整个成年大脑中检测到了GR、MR和11β - HSD2 mRNA表达。虽然在成年大脑中未检测到11β - HSD1表达,但我们在发育中的雀类大脑中检测到了低水平的表达。在几个成年大脑区域中,11β - HSD2的表达与GR和MR共变,但小脑和海马体除外。后两个区域的受体可能需要直接接触全身GC水平。总体而言,这些结果表明11β - HSD2表达通过以背景和区域特异性方式快速代谢GC来保护成年鸣禽大脑。