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 (original) (raw)

2005, The Journal of Steroid Biochemistry and Molecular Biology

7-Hydroxy-metabolites of dehydroepiandrosterone (DHEA) and 3␤,17␤-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␣-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␤-to 7␣-metabolites ranged from 0.6 to 1. These results are consistent with models suggesting 7␣-hydroxylation of the parent steroid, conversion to a 7-oxo-steroid and finally to the 7␤-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.