11-BETA-HYDROXYSTEROID DEHYDROGENASE BIOACTIVITY AND MESSENGER-RNA EXPRESSION IN RAT FOREBRAIN - LOCALIZATION IN HYPOTHALAMUS, HIPPOCAMPUS, AND CORTEX
11-BETA-HYDROXYSTEROID DEHYDROGENASE BIOACTIVITY AND MESSENGER-RNA EXPRESSION IN RAT FOREBRAIN - LOCALIZATION IN HYPOTHALAMUS, HIPPOCAMPUS, AND CORTEX
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DOI：
10.1210/endo-127-3-1450
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发表时间：
1990-09-01
期刊：
影响因子：
4.8
通讯作者：
EDWARDS, CRW
中科院分区：
文献类型：
--
作者：
MOISAN, MP;SECKL, JR;EDWARDS, CRW
在外周醛固酮靶位点（例如，肾），11 β-羟基类固醇脱氢酶（11 β- OHSD）将皮质酮代谢为无活性的11-脱氢皮质酮，从而保护盐皮质激素受体免受体内皮质酮的暴露。我们已经调查了11. beta. OHSD可以解释大鼠脑皮质类固醇受体对皮质酮敏感性的位点特异性差异。在NADP+（200 μ M）存在下，以[3 H]皮质酮转化为[3 H]11-脱氢皮质酮的百分比估算的酶活性为：海马，55.8 ±。2.7%;皮质，52 . ±. 3.1%;垂体; 40 . ±. 2%，下丘脑，26.1 . ±. 1.2%;脑干21.4 ±。脊髓12.3 ± 1.7%。百分之一点八北方印迹，使用来自11 β-来源于大鼠肝脏的OHSD cDNA克隆显示，在与11 β-羟色胺相同大小的所有脑区域中表达单一mRNA种类。肝脏和肾脏中的OHSD mRNA。在海马和皮质中发现最高表达。原位杂交，使用[35 S] UTP标记的cRNA探针，定位高mRNA表达的大脑皮质（特别是顶叶皮质，后IV），海马（最高的CA 3），下丘脑内侧视前区和弓状核和垂体前叶。总之，存在局部11 β。大鼠脑内OHSD mRNA表达及酶活性。11.beta的分布OHSD对应于糖皮质激素或盐皮质激素受体对皮质酮亲和力降低的区域。11. beta.- OHSD可调节皮质酮进入脑盐皮质激素和/或糖皮质激素受体，从而调节皮质类固醇对脑功能的影响。
In peripheral aldosterone target sites (e.g., kidney), 11.beta.-hydroxysteroid dehydrogenase (11.beta.-OHSD) metabolizes corticosterone to inactive 11-dehydrocorticosterone and thus protects mineralocorticoid receptors from exposure to corticosterone in vivo. We have investigated whether 11.beta.-OHSD could account for the site-specific differences in corticosteroid receptor sensitivity to corticosterone in rat brain. Enzyme activity, estimated as the percentage conversion of [3H]corticosterone to [3H]11-dehydrocorticosterone in the presence of NADP+ (200 .mu.M), was: hippocampus, 55.8 .+-. 2.7%; cortex, 52 .+-. 3.1%; pituitary; 40 .+-. 2%, hypothalamus, 26.1 .+-. 1.2%; brain stem, 21.4 .+-. 1.7%; and spinal cord, 12.3 .+-. 1.8%. Northern blots, using [32P]dCTP-labeled probes from an 11.beta.-OHSD cDNA clone derived from rat liver, showed expression of a single mRNA species in all brain areas of identical size to 11.beta.-OHSD mRNA in liver and kidney. Highest expression was found in hippocampus and cortex. In situ hybridization, using [35S]UTP-labeled cRNA probes, localized high mRNA expression to cerebral cortex (particularly parietal cortex, later IV), hippocampus (highest in CA3), hypothalamic medial preoptic area and arcuate nuclei and anterior pituitary. In conclusion, there is localized 11.beta.-OHSD mRNA expression and enzyme bioactivity in rat brain. The distribution of 11.beta.-OHSD corresponds to areas of reduced glucocorticoid or mineralocorticoid receptor affinity for corticosterone. Therefore 11.beta.-OHSD may regulate the access of corticosterone to cerebral mineralcorticoid and/or glucocorticoid receptors and thus modulate corticosteroid effects on brain function.