Moderate doses of ethanol fail to increase plasma levels of neurosteroid 3α-hydroxy-5α-pregnan-20-one-like immunoreactivity in healthy men and women

Abstract

3alpha,5alpha-THP-like immunoreactivity levels in human plasma are not increased following moderate ethanol consumption, suggesting that circulating levels of progesterone or its tetrahydro-reduced metabolites do not play a major role in ethanol action. However, the possibility remains that ethanol increases endogenous brain production of GABAergic neurosteroids without affecting plasma levels. Moreover, humans synthesize 5beta-reduced GABAergic steroids, and levels of these steroids may be altered in plasma or brain.

Subjective effects and changes in steroid hormone concentrations in humans following acute consumption of alcohol

“…First, it is likely that adolescents seeking treatment at the emergency department for alcohol intoxication had higher blood alcohol concentrations than the concentrations produced in the present study or in the study by Holdstock et al (2005). Second, Ortega (2003, 2004) and Holdstock et al (2005) used RIA to measure ALLO concentrations, whereas we used GC/MS, which has greater sensitivity and specificity than RIA (Alomary et al 2001). Third, the serum concentrations of ALLO in the adolescents studied by Ortega (2003, 2004) were higher than that seen in the present study and in other studies (Pearson Murphy and Allison 2000; Genazzani et al 1998).…”

“…Methodological differences may be responsible for the conflicting results in humans. First, it is likely that adolescents seeking treatment at the emergency department for alcohol intoxication had higher blood alcohol concentrations than the concentrations produced in the present study or in the study by Holdstock et al (2005). Second, Ortega (2003, 2004) and Holdstock et al (2005) used RIA to measure ALLO concentrations, whereas we used GC/MS, which has greater sensitivity and specificity than RIA (Alomary et al 2001).…”

“…The findings also differ markedly from those obtained in adolescent men and women suffering from acute alcohol intoxication Ortega 2003, 2004). Further, Holdstock et al (2005) found no effect of alcohol on ALLO concentrations measured by RIA. Methodological differences may be responsible for the conflicting results in humans.…”

“…Earlier studies reported similar effects on PROG among premenopausal women who were not using oral contraceptives (Teoh et al 1990). Although contradictory results have been reported in other studies (McNamee et al 1979;Valimaki et al 1983;Mendelson et al 1989;Martin et al 1999;Garcia-Closas et al 2002;Torres and Ortega 2003;Holdstock et al 2005), most of these studies involved small study samples, resulting in low statistical power. Recently, Hill et al (2005) found depressed PROG and a decreased PROG/PREG ratio in the absence of alcohol administration among premenopausal women undergoing alcoholism treatment.…”

“…These findings raise a question of whether the ALLO assays in the studies by Ortega (2003, 2004) were confounded by cross reactivity with other neuroactive steroids that may be elevated following high-dose alcohol consumption. Indeed, Holdstock et al (2005) report that both low sensitivity of the antibody and cross reactivity may have confounded their results. In rodents, ALLO is thought to modulate the anxiolytic, anticonvulsive, anticonflictive, and rewarding effects of alcohol through allosteric modulation of GABA A receptors (Morrow et al 2001).…”