Department of Physiological Science, University of California, Los Angeles, CA 90095, USA.
Gen Comp Endocrinol. 2010 May 1;166(3):600-5. doi: 10.1016/j.ygcen.2010.01.016. Epub 2010 Feb 1.
The enzyme 11betaHSD2 inactivates glucocorticoids by synthesizing metabolites that bind poorly to mineralocorticoid and glucocorticoid receptors. Oscine songbirds (Passeriformes) are important models for investigating stress hormone effects on brain and behavior but nothing is known about 11betaHSD2 activity in the songbird brain. We measured 11betaHSD2 mRNA expression and enzymatic activity in brain of adult and developing male and female zebra finches. Since 11betaHSD2 plays an important role in GC metabolism in some peripheral organs we measured mRNA and catalytic activity also in the adult liver, kidney colon and gonads. 11betaHSD2 mRNA was detected in all brain regions examined with expression in the cerebellum and hypothalamus greater in females than in males; expression in ovaries was greater than in testes. No differences were detected in the other peripheral tissues. Catalytic activity of 11betaHSD2 could be measured in brain, but at low levels and no sex differences were measured in any region tested. Because 11betaHSD2 protects mineralocorticoid sensitive tissues from inappropriate CORT action, we also measured mineralocorticoid receptor (MR) expression in adult brain kidney and liver. MR mRNA was detected in all tissues with similar levels of expression in neural and peripheral tissues. The wide distribution of 11betaHSD2 and MR throughout the songbird brain suggests that concentrations of glucocorticoids may be locally regulated in brain to modulate their actions on MR and possibly also glucocorticoid receptors (GR). Notable differences between mRNA expression and activity point to post-transcriptional regulation of the 11betaHSD2 enzyme.
11βHSD2 酶通过合成与盐皮质激素和糖皮质激素受体结合能力差的代谢物使糖皮质激素失活。鸣禽（雀形目）是研究应激激素对大脑和行为影响的重要模型，但关于鸣禽大脑中 11βHSD2 活性的信息却一无所知。我们测量了成年和发育中雄性和雌性斑马雀大脑中 11βHSD2 的 mRNA 表达和酶活性。由于 11βHSD2 在一些外周器官的 GC 代谢中发挥着重要作用，我们还测量了成年肝脏、肾脏、结肠和性腺中的 mRNA 和催化活性。在所检查的所有脑区均检测到 11βHSD2 mRNA，小脑和下丘脑的表达在雌性中大于雄性；卵巢中的表达大于睾丸。在其他外周组织中未检测到差异。可以在大脑中测量 11βHSD2 的催化活性，但在任何测试区域都未测量到性别差异，且活性水平较低。由于 11βHSD2 可保护糖皮质激素敏感组织免受 CORT 的不当作用，我们还测量了成年大脑、肾脏和肝脏中的盐皮质激素受体 (MR) 表达。在所有组织中均检测到 MR mRNA，神经和外周组织的表达水平相似。11βHSD2 和 MR 广泛分布于鸣禽大脑中，表明糖皮质激素的浓度可能在大脑中局部调节，以调节其对 MR 以及可能对糖皮质激素受体 (GR) 的作用。mRNA 表达和活性之间的显著差异表明 11βHSD2 酶存在转录后调控。
