Acute ethanol administration to rodents (1.3 - 4.0 g/kg) induces a marked increase in the brain and plasma concentrations of the potent GABAergic neuroactive steroids 3alpha-hydroxy-5alpha-pregnan-20-one (3a,5a-THP) and 3alpha,21-dihydroxy-5alpha-pregnan-20-one (3a,5a-THDOC), but does not alter the androgen steroids dehydroepiandrosterone (DHEA) and its sulfate derivative DHEAS (see Morrow et al., 2006 for review). In contrast, moderate doses of ethanol (0.8 g/kg) have no effect (Holdstock et al., 2006) or decrease plasma 3a,5a-THP concentrations (Pierucci-Lagha et al., 2006) in healthy human subjects, but effects on DHEA levels are controversial (Pierucci-Lagha et al., 2006; Sarkola et al., 2000). We hypothesized that androgen steroids might be more responsive to ethanol consumption in humans compared to rodents. To address this hypothesis we measured DHEA and DHEAS plasma levels in healthy volunteers after acute ethanol consumption. Men (n = 8) and women (n = 12) in the follicular phase of the menstrual cycle were included in the study. Each subject participated in two sessions on which they received ethanol (0.8 g/kg or 0.7 g/kg, respectively for men and women) or placebo. Blood was obtained 15 minutes before and 30, 60, 120 and 375 minutes after ethanol consumption and DHEA and DHEAS were measured in plasma samples by radioimmunoassay. Ethanol decreased DHEAS levels at all time points, compared to the basal sample taken 15 minutes before its consumption. In men, DHEAS levels were decreased by 8 and 11% at 30 and 60 minutes (p < 0.05) and by 15 and 16% at 120 and 375 minutes (p < 0.01). In women, DHEAS levels were decreased by 11% at 30 minutes (p < 0.05) and by 16, 19 and 26% at 60, 120 and 375 minutes respectively (p < 0.001). In contrast, ethanol consumption did not alter DHEA levels in men or women at any of the time points examined. These preliminary data suggest that acute ethanol consumption alters DHEAS, but not DHEA levels in human subjects. Thus, it is possible that DHEA is rapidly metabolized into its androgen derivatives; future studies will address this hypothesis. Supported by AA10564, AA13515 (ALM) and DA02812 (HDW).

Acute ethanol consumption decreases DHEAS levels in healthy men and women, without changing DHEA levels

Porcu P;
2007-01-01

Abstract

Acute ethanol administration to rodents (1.3 - 4.0 g/kg) induces a marked increase in the brain and plasma concentrations of the potent GABAergic neuroactive steroids 3alpha-hydroxy-5alpha-pregnan-20-one (3a,5a-THP) and 3alpha,21-dihydroxy-5alpha-pregnan-20-one (3a,5a-THDOC), but does not alter the androgen steroids dehydroepiandrosterone (DHEA) and its sulfate derivative DHEAS (see Morrow et al., 2006 for review). In contrast, moderate doses of ethanol (0.8 g/kg) have no effect (Holdstock et al., 2006) or decrease plasma 3a,5a-THP concentrations (Pierucci-Lagha et al., 2006) in healthy human subjects, but effects on DHEA levels are controversial (Pierucci-Lagha et al., 2006; Sarkola et al., 2000). We hypothesized that androgen steroids might be more responsive to ethanol consumption in humans compared to rodents. To address this hypothesis we measured DHEA and DHEAS plasma levels in healthy volunteers after acute ethanol consumption. Men (n = 8) and women (n = 12) in the follicular phase of the menstrual cycle were included in the study. Each subject participated in two sessions on which they received ethanol (0.8 g/kg or 0.7 g/kg, respectively for men and women) or placebo. Blood was obtained 15 minutes before and 30, 60, 120 and 375 minutes after ethanol consumption and DHEA and DHEAS were measured in plasma samples by radioimmunoassay. Ethanol decreased DHEAS levels at all time points, compared to the basal sample taken 15 minutes before its consumption. In men, DHEAS levels were decreased by 8 and 11% at 30 and 60 minutes (p < 0.05) and by 15 and 16% at 120 and 375 minutes (p < 0.01). In women, DHEAS levels were decreased by 11% at 30 minutes (p < 0.05) and by 16, 19 and 26% at 60, 120 and 375 minutes respectively (p < 0.001). In contrast, ethanol consumption did not alter DHEA levels in men or women at any of the time points examined. These preliminary data suggest that acute ethanol consumption alters DHEAS, but not DHEA levels in human subjects. Thus, it is possible that DHEA is rapidly metabolized into its androgen derivatives; future studies will address this hypothesis. Supported by AA10564, AA13515 (ALM) and DA02812 (HDW).
2007
neuroactive steroids
DHEA
ethanol
humans
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/297822
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