Acutely administered ethanol participates in testosterone synthesis and increases testosterone in rat brain

Background: The interaction of alcohol and testosterone has long been of interest, mainly due to the effect of alcohol on aggression and sexual behavior. To date, there have been very few, if any, studies examining the effect of acute alcohol administration on testosterone concentrations in the brain. The administration of 1,1-dideuteroethanol ([1,1-H-2(2)]ethanol) provided the opportunity to trace the deuterium label into newly synthesized deuterotestosterone in brain samples to determine whether ethanol oxidation was directly linked to testosterone synthesis. Methods: Unoperated and adrenalectomized-gonadectomized (ADX/GDX) rats were given either ethanol or [1,1-H-2(2)]ethanol in a single intraperitoneal dose of 2 g/kg body weight. We used gas chromatography/mass spectrometry to accurately determine both the amount of steroids present and the degree of deuterium incorporation into specific steroids isolated from brain samples. Results: Thirty minutes after alcohol administration, the level of total testosterone increased 4-fold in the frontal cortex and 3-fold in the plasma of unoperated male Wistar rats. The relative increase in the abundance of monodeuterated testosterone 30 min after [1,1-H-2(2)]ethanol administration was significant (p < 0.05) in both brain and plasma. ADX/GDX animals treated with alcohol had testosterone concentrations that were 5% of those found in unoperated animals dosed with ethanol. Conclusions: Acutely administered ethanol increased brain concentrations of testosterone 4-fold in male Wistar rats. ADX/GDX surgery reduced brain concentrations of testosterone in response to alcohol by 95%. The deuterium labeling of testosterone after [1,1-H-2(2)]ethanol showed that ethanol oxidation is directly linked to testosterone biosynthesis and that the deuterium-labeled testosterone is present in the central nervous system. These results demonstrate that peripherally administered ethanol directly contributes to the concentrations of testosterone in the central nervous system and that the testosterone found in brain samples is primarily synthesized in the periphery. These findings may be important for understanding the behavioral changes associated with acute alcohol consumption.