Jamieson P M, Chapman K E, Seckl J R
Molecular Endocrinology, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Scotland, UK.
J Steroid Biochem Mol Biol. 1999 Mar;68(5-6):245-50. doi: 10.1016/s0960-0760(99)00037-0.
11Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) catalyses the interconversion of active corticosterone and inert 11-dehydrocorticosterone. Short-term glucocorticoid excess upregulates 11beta-HSD-1 in liver and hippocampus leading to suggestions that 11beta-HSD-1 ameliorates the deleterious effects of glucocorticoid excess by its 11beta-dehydrogenase activity. However the predominant activity of 11beta-HSD-1 in vivo is 11beta-reduction, thus generating active glucocorticoid. We have re-examined the time-course of glucocorticoid regulation of 11beta-HSD-1 in the liver, hippocampus and kidney of adult male rats in vivo. Sham operation markedly reduced 11beta-HSD-1 mRNA expression in all tissues, and reduced 11beta-HSD bioactivity in liver and hippocampus when compared to untouched controls. Adrenalectomy reduced 11beta-HSD-1 expression in all tissues in the short-term (7 days), followed by subsequent recovery of enzyme activity by 21 days in liver and hippocampus. Dexamethasone replacement of adrenalectomised rats attenuated the initial decrease in hepatic 11beta-HSD-1 activity, but by 21 days dexamethasone reduced activity compared to control levels. Thus glucocorticoids regulate 11beta-HSD-1 in a complex tissue- and temporal-specific manner. This pattern of regulation suggests glucocorticoids repress 11beta-HSD-1 at least in the liver, a pattern of regulation more consistent with the evidence that 11beta-HSD-1 is an 11beta-reductase in vivo. Operational stress per se down-regulates 11beta-HSD-1 which has implications for interpretation and design of in vivo studies of 11beta-HSD-1.
11β-羟类固醇脱氢酶1型（11β-HSD-1）催化活性皮质酮与无活性11-脱氢皮质酮的相互转化。短期糖皮质激素过量会使肝脏和海马体中的11β-HSD-1上调，这表明11β-HSD-1通过其11β-脱氢酶活性减轻了糖皮质激素过量的有害影响。然而，11β-HSD-1在体内的主要活性是11β-还原，从而生成活性糖皮质激素。我们重新研究了成年雄性大鼠体内肝脏、海马体和肾脏中糖皮质激素对11β-HSD-1调节的时间进程。假手术显著降低了所有组织中11β-HSD-1 mRNA的表达，与未处理的对照组相比，降低了肝脏和海马体中的11β-HSD生物活性。肾上腺切除在短期内（7天）降低了所有组织中11β-HSD-1的表达，随后肝脏和海马体中的酶活性在21天时恢复。用 dexamethasone替代肾上腺切除的大鼠减弱了肝脏中11β-HSD-1活性的最初下降，但到21天时，dexamethasone使活性低于对照水平。因此，糖皮质激素以复杂的组织和时间特异性方式调节11β-HSD-1。这种调节模式表明糖皮质激素至少在肝脏中抑制11β-HSD-1，这种调节模式与11β-HSD-1在体内是一种11β-还原酶的证据更一致。手术应激本身会下调11β-HSD-1，这对11β-HSD-1体内研究的解释和设计有影响。
