The identification and simultaneous quantification of 7-hydroxylated metabolites of pregnenolone, dehydroepiandrosterone, 3beta,17beta-androstenediol, and testosterone in human serum using gas chromatography-mass spectrometry.
7-Hydroxy-metabolites of dehydroepiandrosterone (DHEA) and 3beta,17beta-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 7alpha-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 7beta- to 7alpha-metabolites ranged from 0.6 to 1. These results are consistent with models suggesting 7alpha-hydroxylation of the parent steroid, conversion to a 7-oxo-steroid and finally to the 7beta-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.
Hill
Martin
M
Institute of Endocrinology, Národní trída 8, CZ 116 94 Prague, Czech Republic. mhill@endo.cz
Havlíková
Helena
H
Vrbíková
Jana
J
Kancheva
Radmila
R
Kancheva
Lyudmila
L
Pouzar
Vladimír
V
Cerný
Ivan
I
Stárka
Luboslav
L
D000293:Adolescent; D000328:Adult; D015114:Androstenediol / Q000031:analogs & derivatives* / Q000097:blood*; D002648:Child; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000097:blood*; D005260:Female; D005498:Follicular Phase; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006900:Hydroxylation; D008297:Male; D011284:Pregnenolone / Q000031:analogs & derivatives* / Q000097:blood*; D012016:Reference Values; D013739:Testosterone / Q000031:analogs & derivatives* / Q000097:blood*
D013739:Testosterone; D003687:Dehydroepiandrosterone; D011284:Pregnenolone; D015114:Androstenediol