Attal-Khémis S, Dalmeyda V, Michot J L, Roudier M, Morfin R
Conservatoire National des Arts et Métiers, Paris, France.
J Gerontol A Biol Sci Med Sci. 1998 Mar;53(2):B125-32. doi: 10.1093/gerona/53a.2.b125.
Evidence has indicated that circulating adrenal steroid quantitites were significantly changed in patients with Alzheimer's disease (AD). Aside of 3 beta-sulfatation and 3 beta-acylations, levels of dehydroepiandrosterone (DHEA) result from production and metabolic transformation yields. 7 alpha-Hydroxylation of DHEA has been described in humans, and 7 alpha-hydroxy-DHEA may be responsible for the known antiglucocorticoid effects of DHEA. Using a negative ion fragmentometry method with gas chromatography/mass spectrometry on trifluoroacetate derivatives, we measured levels of free 7 alpha-hydroxy-DHEA as well as its sulfated conjugate and its fatty acid esters in serum of 10 female patients with AD and of 8 age-matched healthy control women. Free 7 alpha-hydroxy-DHEA levels in AD and controls were not significantly different (240.2 +/- 37.2 pg/ml and 206.8 +/- 21.6 pg/ml, respectively), but sulfate conjugate levels were significantly increased in AD (p = .01) (262 +/- 28.4 and 145.4 +/- 27.6, respectively) as well as fatty acid esters (p = .041) (65.7 +/- 6.9 and 40.7 +/- 9.2, respectively). These results indicated that the total 7 alpha-hydroxy-DHEA produced was significantly increased in AD (p = .024) and may contribute to the disease-related disturbances of DHEA production and metabolism.
有证据表明,阿尔茨海默病(AD)患者体内循环肾上腺类固醇的含量发生了显著变化。除了3β-硫酸化和3β-酰化作用外,脱氢表雄酮(DHEA)的水平还取决于其产生和代谢转化的产量。人类体内已发现DHEA存在7α-羟基化作用,7α-羟基-DHEA可能是DHEA已知的抗糖皮质激素作用的原因。我们采用气相色谱/质谱联用的负离子碎片分析法,对三氟乙酸衍生物进行分析,测定了10名女性AD患者和8名年龄匹配的健康对照女性血清中游离7α-羟基-DHEA及其硫酸化共轭物和脂肪酸酯的水平。AD患者和对照组的游离7α-羟基-DHEA水平无显著差异(分别为240.2±37.2 pg/ml和206.8±21.6 pg/ml),但AD患者的硫酸化共轭物水平显著升高(p = 0.01)(分别为262±28.4和145.4±27.6),脂肪酸酯水平也显著升高(p = 0.041)(分别为65.7±6.9和40.7±9.2)。这些结果表明,AD患者体内产生的总7α-羟基-DHEA显著增加(p = 0.024),可能导致了与疾病相关的DHEA产生和代谢紊乱。