title: Increased steroid hormone dehydroepiandrosterone and pregnenolone levels in post-mortem brain samples of alcoholics.
abstract: Intra-tissue levels of steroid hormones (e.g., dehydroepiandrosterone [DHEA], pregnenolone [PREGN], and testosterone [T]) may influence the pathological changes seen in neurotransmitter systems of alcoholic brains. Our aim was to compare levels of these steroid hormones between the post-mortem brain samples of alcoholics and non-alcoholic controls. We studied steroid levels with quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) in post-mortem brain samples of alcoholics (N = 14) and non-alcoholic controls (N = 10). Significant differences were observed between study groups in DHEA and PREGN levels (p values 0.0056 and 0.019, respectively), but not in T levels. Differences between the study groups were most prominent in the nucleus accumbens (NAC), anterior cingulate cortex (ACC), and anterior insula (AINS). DHEA levels were increased in most alcoholic subjects compared to controls. However, only a subgroup of alcoholics showed increased PREGN levels. Negative Spearman correlations between tissue levels of PREGN and previous reports of [(3)H]naloxone binding to μ-opioid receptors were observed in the AINS, ACC, NAC, and frontal cortex (R values between -0.6 and -0.8; p values ≤ 0.002), suggesting an association between the opioid system and brain PREGN levels. Although preliminary, and from relatively small diagnostic groups, these results show significantly increased levels of DHEA and PREGN in the brains of alcoholics, and could be associated with the pathology of alcoholism.
authors.affiliation: Pharmacology and Toxicology, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland. Electronic address: olli.karkkainen@uef.fi.
authors.forename: Olli
authors.initials: O
authors.lastname: Kärkkäinen
authors.affiliation: Pharmaceutical Chemistry, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Merja R
authors.initials: MR
authors.lastname: Häkkinen
authors.affiliation: Pharmaceutical Chemistry, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Auriola
authors.affiliation: General Practice, University of Helsinki, FI-00014 Helsinki, Finland; Unit of Primary Health Care, Kuopio University Hospital, FI-70029 Kuopio, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Kautiainen
authors.affiliation: Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, FI-70240 Kuopio, Finland; Clinical Neuroscience, Karolinska Institutet, S-171 76 Stockholm, Sweden.
authors.forename: Jari
authors.initials: J
authors.lastname: Tiihonen
authors.affiliation: Pharmacology and Toxicology, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Markus
authors.initials: M
authors.lastname: Storvik
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000378:metabolism* / Q000473:pathology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D003687:Dehydroepiandrosterone / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011284:Pregnenolone / Q000378:metabolism*; D055815:Young Adult
chemical_list: D003687:Dehydroepiandrosterone; D011284:Pregnenolone
keywords: Anterior cingulate cortex; Anterior insula; DHEA; Pregnenolone; Testosterone; μ-opioid receptor