Endogenous synthesis of corticosteroids in the hippocampus.
Endogenous synthesis of corticosteroids in the hippocampus.
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DOI：
10.1371/journal.pone.0021631
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Kawato S
中科院分区：
文献类型：
--
作者：
Higo S;Hojo Y;Ishii H;Komatsuzaki Y;Ooishi Y;Murakami G;Mukai H;Yamazaki T;Nakahara D;Barron A;Kimoto T;Kawato S
包括性类固醇在内的脑内类固醇合成备受关注。然而，由于无法检测到脱氧皮质酮（DOC）合成酶细胞色素P450(c21)，海马体内皮质类固醇的内源性合成一直受到怀疑。用mRNA分析和免疫金电镜分析证实了P450（c21）在成年雄性大鼠海马中的表达。通过3h -甾体代谢分析证实了孕酮（PROG）产生DOC。原位杂交和免疫电镜分析显示，所有皮质类固醇合成所需的酶，包括P450（c21）、P450（2D4）、P450（11β1）和3β-羟基类固醇脱氢酶（3β-HSD）都定位于海马主神经元。采用液相色谱-串联质谱法准确测定大鼠海马皮质类固醇浓度。肾上腺切除大鼠海马净合成皮质酮（CORT）和DOC分别为6.9 nM和5.8 nM。低纳摩尔（10 nM）剂量的CORT作用1小时后，海马的脊髓发生增强。这表明皮质类固醇在海马神经元中合成“孕烯醇酮→PROG→DOC→CORT”的完整途径。P450（c21）和P450（2D4）都能催化PROG转化为DOC。海马神经元合成的低纳摩尔水平的CORT可能在突触可塑性的调节中发挥作用，而不是来自肾上腺的微摩尔水平的CORT的应激作用。
Brain synthesis of steroids including sex-steroids is attracting much attention. The endogenous synthesis of corticosteroids in the hippocampus, however, has been doubted because of the inability to detect deoxycorticosterone (DOC) synthase, cytochrome P450(c21). The expression of P450(c21) was demonstrated using mRNA analysis and immmunogold electron microscopic analysis in the adult male rat hippocampus. DOC production from progesterone (PROG) was demonstrated by metabolism analysis of 3H-steroids. All the enzymes required for corticosteroid synthesis including P450(c21), P450(2D4), P450(11β1) and 3β-hydroxysteroid dehydrogenase (3β-HSD) were localized in the hippocampal principal neurons as shown via in situ hybridization and immunoelectron microscopic analysis. Accurate corticosteroid concentrations in rat hippocampus were determined by liquid chromatography-tandem mass spectrometry. In adrenalectomized rats, net hippocampus-synthesized corticosterone (CORT) and DOC were determined to 6.9 and 5.8 nM, respectively. Enhanced spinogenesis was observed in the hippocampus following application of low nanomolar (10 nM) doses of CORT for 1 h. These results imply the complete pathway of corticosteroid synthesis of ‘pregnenolone →PROG→DOC→CORT’ in the hippocampal neurons. Both P450(c21) and P450(2D4) can catalyze conversion of PROG to DOC. The low nanomolar level of CORT synthesized in hippocampal neurons may play a role in modulation of synaptic plasticity, in contrast to the stress effects by micromolar CORT from adrenal glands.
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影响因子：
4.8
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