REGULATION OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITY IN HUMAN SKIN FIBROBLASTS - ENZYMATIC MODULATION OF GLUCOCORTICOID ACTION
REGULATION OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITY IN HUMAN SKIN FIBROBLASTS - ENZYMATIC MODULATION OF GLUCOCORTICOID ACTION
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DOI：
10.1210/jcem-73-2-326
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发表时间：
1991-08-01
影响因子：
5.8
通讯作者：
SIITERI, PK
中科院分区：
文献类型：
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作者：
HAMMAMI, MM;SIITERI, PK
在培养的人皮肤成纤维细胞中研究了11-β-羟基类固醇脱氢酶（11-β-HSD）的调节。11-氧化还原酶活性比11-β-脱氢酶活性高5 - 10倍。用100 nM地塞米松（Dex）处理的细胞显示两种活性的最大速度增加了3倍，而K（m）值没有变化。地塞米松诱导的11-β-HSD在48小时达到最大值的一半，并被糖皮质激素受体拮抗剂阻断。非糖皮质激素类激素无效。从培养基中去除血清增加最大速度值高达6倍。用8-溴-cAMP、佛波醇酯或胰岛素处理在没有血清的情况下生长的细胞降低了11-β-HSD的活性。地塞米松处理和血清清除的效果是加和的，并被放线菌酮和放线菌素D阻断。在所有实验中，11-β-HSD活性均平行调节。可的松（200 nM）和皮质醇增加血清存在下的成纤维细胞的芳香化酶活性。我们的结论是：1）在人成纤维细胞中，11-β-HSD似乎是一种受多因素调节的单一蛋白质; 2）11-β-HSD可能增加或减少皮质醇对糖皮质激素受体的利用率;和3）血浆可的松水平在评估糖皮质激素状态中可能是重要的。
The regulation of 11-beta-hydroxysteroid dehydrogenase (11-beta-HSD) was studied in cultured human skin fibroblasts. 11-Oxo-reductase activity was 5- to 10-fold higher than 11-beta-dehydrogenase activity. Cells treated with 100 nM dexamethasone (Dex) showed a 3-fold increase in the maximum velocity of both activities without a change in the K(m) values. Dex induction of 11-beta-HSD was half-maximal at 48 h and was blocked by glucocorticoid receptor antagonists. Nonglucocorticoid steroids were ineffective. Removal of serum from the culture medium increased maximum velocity values up to 6-fold. Treatment of cells grown in the absence of serum with 8-bromo-cAMP, phorbol esters, or insulin decreased both 11-beta-HSD activities. The effects of Dex treatment and serum removal were additive and were blocked by cycloheximide and actinomycin-D. In all experiments both 11-beta-HSD activities were modulated in parallel. Both cortisone (200 nM) and cortisol increased the aromatase activity of fibroblasts in the presence of serum. Prior induction of 11-beta-HSD by serum removal increased the potency of cortisone from 10-15% to 50% that of cortisol.We conclude that 1) in human fibroblasts 11-beta-HSD appears to be a single protein that is under multifactorial regulation; 2) 11-beta-HSD may increase or decrease cortisol availability to glucocorticoid receptors; and 3) plasma cortisone levels may be important in assessing glucocorticoid status.