CYP17A1和3β-羟基类固醇脱氢酶在神经系统细胞中的表达和调节：维生素D对脑类固醇生成的潜在作用。,Neurochemistry international

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CYP17A1和3β-羟基类固醇脱氢酶在神经系统细胞中的表达和调节：维生素D对脑类固醇生成的潜在作用。
Neurochemistry international ( IF 4.4 ) Pub Date : 2017-11-23 , DOI: 10.1016/j.neuint.2017.11.007
Ida Emanuelsson ₁ , Mokhtar Almokhtar ₁ , Kjell Wikvall ₁ , Alfhild Grönbladh ₁ , Erik Nylander ₁ , Anne-Lie Svensson ₁ , Åsa Fex Svenningsen ₂ , Maria Norlin ₁

Affiliation

据报道类固醇在神经系统中具有多种功能。已经报道了在包括星形胶质细胞和神经元在内的不同细胞类型中酶促产生类固醇激素。但是，有关某些类固醇生成酶的信息在许多方面是不够的。关于在神经系统中不同细胞类型对CYP17A1和3β-羟基类固醇脱氢酶（3β-HSD）表达的相对重要性的报道矛盾的结果。3β-HSD在所有基本类固醇生成途径中都很重要，并且需要CYP17A1来形成性激素。在当前的研究中，我们研究了这些酶在培养的原代大鼠星形胶质细胞，大鼠大脑皮层的神经元富集细胞以及人神经母细胞瘤SH-SY5Y细胞中的表达，通常用作神经元功能和分化的体外模型的细胞系。作为这项研究的一部分，我们还研究了维生素D对CYP17A1和3β-HSD的潜在作用，该化合物先前已证明对大脑外产生类固醇激素的细胞具有调节作用。我们的研究结果表明，星形胶质细胞是3β-HSD表达的主要位点，而在星形胶质细胞和神经元中都发现了CYP17A1的表达。当前数据表明，与先前的某些报道相反，神经元不参与3β-HSD反应。先前的研究表明，维生素D可以通过某些细胞中的类固醇生成酶影响基因表达和激素产生。我们发现维生素D在SH-SY5Y细胞和星形胶质细胞中抑制CYP17A1介导的活性达20％。CYP17A1 mRNA水平的抑制作用要强得多，在SH-SY5Y细胞中约为50％，在星形胶质细胞中约为75％。在星形胶质细胞中，维生素D也抑制了3β-HSD，在酶活性水平上约为20％，在mRNA水平上约为60％。这些数据表明，维生素D介导的CYP17A1和3β-HSD调节，特别是在转录水平上，可能在神经系统中起作用。

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Expression and regulation of CYP17A1 and 3β-hydroxysteroid dehydrogenase in cells of the nervous system: Potential effects of vitamin D on brain steroidogenesis.

Steroids are reported to have diverse functions in the nervous system. Enzymatic production of steroid hormones has been reported in different cell types, including astrocytes and neurons. However, the information on some of the steroidogenic enzymes involved is insufficient in many respects. Contradictory results have been reported concerning the relative importance of different cell types in the nervous system for expression of CYP17A1 and 3β-hydroxysteroid dehydrogenase (3β-HSD). 3β-HSD is important in all basic steroidogenic pathways and CYP17A1 is required to form sex hormones. In the current investigation we studied the expression of these enzymes in cultured primary rat astrocytes, in neuron-enriched cells from rat cerebral cortex and in human neuroblastoma SH-SY5Y cells, a cell line often used as an in vitro model of neuronal function and differentiation. As part of this study we also examined potential effects on CYP17A1 and 3β-HSD by vitamin D, a compound previously shown to have regulatory effects in steroid hormone-producing cells outside the brain. The results of our study indicate that astrocytes are a major site for expression of 3β-HSD whereas expression of CYP17A1 is found in both astrocytes and neurons. The current data suggest that neurons, contrary to some previous reports, are not involved in 3β-HSD reactions. Previous studies have shown that vitamin D can influence gene expression and hormone production by steroidogenic enzymes in some cells. We found that vitamin D suppressed CYP17A1-mediated activity by 20% in SH-SY5Ycells and astrocytes. Suppression of CYP17A1 mRNA levels was considerably stronger, about 50% in SH-SY5Y cells and 75% in astrocytes. In astrocytes 3β-HSD was also suppressed by vitamin D, about 20% at the enzyme activity level and 60% at the mRNA level. These data suggest that vitamin D-mediated regulation of CYP17A1 and 3β-HSD, particularly on the transcriptional level, may play a role in the nervous system.

更新日期：2017-11-21

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