Serum Profiles of Free and Conjugated Neuroactive Pregnanolone Isomers in Nonpregnant Women of Fertile Age

Background: Pregnanolone isomers (PI) with a hydroxy group in the 3α-position are neuroinhibitors operating via positive modulation of GABAA receptors. The 3β-PI and sulfates of PI and pregnenolone exert the opposite effect. In addition to the brain’s in situ synthesis, some circulating steroids can penetrate the blood-brain barrier. Methods: To assess the physiological impact of peripheral endogenous neuroactive pregnanolone isomers and their polar conjugates in women, serum allopregnanolone (P3α5α), isopregnanolone (P3β5α), pregnanolone (P3α5β), epipregnanolone (P3β5β), pregnenolone, estradiol (including their polar conjugates), and additional steroids were measured in 16 women in the follicular and luteal phases of the menstrual cycle using gas chromatography/mass spectrometry and RIA for the analysis. Linear models and Spearman’s correlations were used for data evaluation. Results and Discussion: The levels of conjugated PI were from one to almost three orders of magnitude higher in comparison with th...