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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Pregnenolone sulfate in the brain: a controversial neurosteroid.
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Pregnenolone sulfate in the brain: a controversial neurosteroid.

机译：大脑中的硫酸孕烯醇酮：一种有争议的神经类固醇。

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Pregnenolone sulfate (PREGS) has been shown, either at high nanomolar or at micromolar concentrations, to increase neuronal activity by inhibiting GABAergic and by stimulating glutamatergic neurotransmission. PREGS is also a potent modulator of sigma type 1 (sigma1) receptors. It has been proposed that these actions of PREGS underlie its neuropharmacological effects, and in particular its influence on memory processes. On the other hand, the PREGS-mediated increase in neuronal excitability may become dangerous under particular conditions, for example in the case of excitotoxic stress or convulsions. However, the physiopathological significance of these observations has recently been put into question by the failure to detect significant levels of PREGS within the brain and plasma of rats and mice, either by direct analytical methods based on liquid chromatography/mass spectrometry (LC/MS) or enzyme linked immunosorbent assay (ELISA) with specific antibodies against PREGS, or by indirect gas chromatography/mass spectrometry (GC/MS) analysis with improved sample workup. These recent results have not come to the attention of a large number of neurobiologists interested in steroid sulfates. However, although available direct analytical methods have failed to detect levels of PREGS above 0.1-0.3 ng/g in brain tissue, it may be premature to completely exclude the local formation of biologically active PREGS within specific and limited compartments of the nervous system. In contrast to the situation in rodents, significant levels of sulfated 3beta-hydroxysteroids have been measured in human plasma and brain. Previous indirect measures of steroid sulfates by radioimmunoassays (RIA) or GC/MS had detected elevated levels of PREGS in rodent brain. The discrepancies between the results of different assay procedures have revealed the danger of indirect analysis of steroid sulfates. Indeed, PREGS must be solvolyzed/hydrolyzed prior to RIA or GC/MS analysis, and it is the released, unconjugated PREG which is then quantified. Extreme caution needs to be exercised during the preparation of samples for RIA or GC/MS analysis, because the fraction presumed to contain only steroid sulfates can be contaminated by nonpolar components from which PREG is generated by the solvolysis/hydrolysis/derivatization reactions.
机译：硫酸孕烯醇酮（PREGS）已显示，无论是高纳摩尔浓度还是微摩尔浓度，都可以通过抑制GABA能和刺激谷氨酸能神经传递来增加神经元活性。 PREGS还是sigma 1型（sigma1）受体的有效调节剂。已经提出，PREGS的这些作用是其神经药理作用尤其是对记忆过程的影响的基础。另一方面，在特定条件下，例如在兴奋毒性应激或惊厥的情况下，PREGS介导的神经元兴奋性增加可能变得危险。但是，最近通过基于液相色谱/质谱（LC / MS）的直接分析方法未能检测到大鼠和小鼠的大脑和血浆中显着水平的PREGS，使这些观察结果的生理病理意义受到质疑。或使用抗PREGS的特异性抗体的酶联免疫吸附测定（ELISA），或通过间接气相色谱/质谱（GC / MS）分析来改善样品处理。这些最新结果尚未引起对类固醇硫酸盐感兴趣的大量神经生物学家的注意。然而，尽管可用的直接分析方法未能检测到脑组织中PREGS的水平超过0.1-0.3 ng / g，但完全排除在神经系统的特定和有限区域内生物活性PREGS的局部形成可能为时过早。与啮齿动物的情况相反，已在人血浆和大脑中检测到大量的硫酸化3β-羟基类固醇。以前通过放射免疫测定法（RIA）或GC / MS间接测定类固醇硫酸盐的水平已检测到啮齿类动物脑中PREGS的水平升高。不同测定方法结果之间的差异表明，存在间接分析类固醇硫酸盐的危险。实际上，在进行RIA或GC / MS分析之前，必须将PREGS溶剂化/水解，然后对释放的未结合的PREG进行定量。在制备用于RIA或GC / MS分析的样品时，必须格外小心，因为假定仅包含类固醇硫酸盐的级分会被溶剂分解/水解/衍生化反应所产生的PREG的非极性成分所污染。

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