The identification and simultaneous quantification of 7-hydroxylated metabolites of pregnenolone, dehydroepiandrosterone, 3β,17β-androstenediol, and testosterone in human serum using gas chromatography-mass spectrometry

被引:23
作者
Hill, M [1 ]
Havlílová, H
Vrbílová, J
Kancheva, R
Kancheva, L
Pouzar, V
Cerny, I
Stárka, L
机构
[1] Inst Endocrinol, Narodni Trida 8, CZ-11694 Prague, Czech Republic
[2] Acad Sci Czech Republic, Inst Organ Chem & Biochem, CR-16610 Prague, Czech Republic
关键词
7-hydroxy steroids; GC-MS; neuroprotective steroids; immunomodulatory steroids; ergosteroids;
D O I
10.1016/j.jsbmb.2005.02.009
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
7-Hydroxy-metabolites of dehydroepiandrosterone (DHEA) and 3 beta,17 beta-androstenediol (AD) possess immunomodulatory and neuroprotective properties; therefore, the measurement of these steroids in patients with autoimmune diseases or disturbances in the CNS may be of interest. A gas chromatography-mass spectrometry (GC-MS) method for the determination of 7-hydroxy-metabolites of pregnenolone, DHEA, AD, and testosterone including the parent steroids was applied to serum samples from 12 adult men (27-66 years), 13 male adolescents (13-20 years), 5 boys (6-10 years), 15 women in the follicular phase of the menstrual cycle (22-45 years), 17 women in the luteal phase (22-45 years), and 4 girls (6-10 years) The steroids were age and sex dependent, but independent of the menstrual cycle. The ratio of the 7 alpha-hydroxy-metabolites to their parent steroids were age dependent, exhibiting an increasing trend (p < 0.0001, ANOVA) from pregnenolone (5%) to AD (20%). The ratio of 7 beta- to 7 alpha-metabolites ranged from 0.6 to 1. These results are consistent with models suggesting 7 alpha-hydroxylation of the parent steroid, conversion to a 7-oxo-steroid and finally to the 7 beta-hydroxylated-metabolite. Partial correlations suggested that 7-hydroxylation might reduce the concentration of circulating androgens. Despite the three times lower concentration of AD-metabolites, their antiglucocorticoid, immunomodulatory, and neuroprotective effects may be comparable to that of DHEA based on their reported greater biological activity. (c) 2005 Elsevier Ltd. All rights reserved.
引用
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页码:187 / 200
页数:14
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