Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, 1-185, Kohasu, Oko-cho, Nankoku City, Kochi 783-8505, Japan; Health Care Center, Kochi University, 1-5-2, Akebono-cho, Kochi City, Kochi 780-8520, Japan.
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, 1-185, Kohasu, Oko-cho, Nankoku City, Kochi 783-8505, Japan.
Steroids. 2022 Jul;183:109021. doi: 10.1016/j.steroids.2022.109021. Epub 2022 Mar 23.
The 11β hydroxysteroid dehydrogenase type-1 (11βHSD-1) is a predominant 11β-reductase regenerating bioactive glucocorticoids (cortisol, corticosterone) from inactive 11-keto forms (cortisone, dehydrocorticosterone), expressed mainly in the brain, liver and adipose tissue. Although the expression levels of 11β HSD-1 mRNA are known to be influenced by glucocorticoids, its tissue-specific regulation is not completely elucidated. In this study, we examined the effect of persistent glucocorticoid excess on the expression of 11β HSD-1 mRNA in the hippocampus, liver, and abdominal adipose tissue in vivo using quantitative real-time PCR. We found that, in C57BL/6J mice treated with corticosterone (CORT) pellet for 2 weeks, 11β HSD-1 mRNA decreased in the hippocampus (HIPP) and liver, whereas it increased in the abdominal fat (FAT), compared with placebo treatment [HIPP: placebo 1.00 ± 0.14, CORT 0.63 ± 0.04; liver: placebo 1.00 ± 0.08, CORT 0.73 ± 0.06; FAT: placebo 1.00 ± 0.16, CORT 2.26 ± 0.39]. Moreover, in CRH transgenic mice, an animal model of Cushing's syndrome with high plasma CORT level, 11β HSD-1 mRNA was also decreased in the hippocampus and liver, and increased in the abdominal adipose tissue compared to that in wild-type mice. These changes were reversed after adrenalectomy in CRH-Tg mice. Altogether, these results reveal the differential regulation of 11β HSD-1 mRNA by glucocorticoid among the tissues examined.
11β 羟甾类脱氢酶 1 型（11βHSD-1）是一种主要的 11β-还原酶，可将无活性的 11-酮形式（可的松、去氢皮质酮）转化为有生物活性的糖皮质激素（皮质醇、皮质酮），主要在脑、肝和脂肪组织中表达。尽管已知 11βHSD-1mRNA 的表达水平受糖皮质激素的影响，但它的组织特异性调节尚未完全阐明。在这项研究中，我们使用定量实时 PCR 检查了持续的糖皮质激素过多对体内海马体、肝脏和腹部脂肪组织中 11βHSD-1mRNA 表达的影响。我们发现，在接受皮质酮（CORT）微球治疗 2 周的 C57BL/6J 小鼠中，与安慰剂治疗相比，海马体（HIPP）和肝脏中的 11βHSD-1mRNA 减少，而腹部脂肪（FAT）中的 11βHSD-1mRNA 增加[HIPP：安慰剂 1.00±0.14，CORT 0.63±0.04；肝脏：安慰剂 1.00±0.08，CORT 0.73±0.06；FAT：安慰剂 1.00±0.16，CORT 2.26±0.39]。此外，在 CRH 转基因小鼠中，一种具有高血浆 CORT 水平的库欣综合征动物模型中，与野生型小鼠相比，海马体和肝脏中的 11βHSD-1mRNA 也减少，而腹部脂肪中的 11βHSD-1mRNA 增加。在 CRH-Tg 小鼠中进行肾上腺切除术可逆转这些变化。总之，这些结果揭示了糖皮质激素在不同组织中对 11βHSD-1mRNA 的差异调节。
