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Radmila Kancheva, Martin Hill, David Cibula¹, Helena Veláková, Lyudmila Kancheva, Jana Vrbíková, Tomá Fait¹, Antonín Paízek¹

Institute of Endocrinology, Národnítída 8, CZ 116 94 Prague 1, Czech Republic
¹ Department of Gynecology and Obstetrics, 1st Medical Faculty, Charles University, Apolináská 18, CZ 128 51 Prague 2, Czech Republic

(Requests for offprints should be addressed to M Hill; Email: mhill{at}endo.cz)

Pregnanolone isomers (PIs) and their polar conjugates (PICs) modulate ionotropic receptors such as -aminobutyric acid or pregnane X receptors. Besides, brain synthesis, PI penetrates the blood–brain barrier. We evaluated the physiological importance of PI respecting the status of sex, menstrual cycle, and pregnancy. Accordingly, circulating levels of allopregnanolone (P3 5 ), isopregnanolone (P3ß 5 ), pregnanolone (P3 5ß ), epipregnanolone (P3ß 5ß ), their polar conjugates, and related steroids were measured in 15 men (M), 15 women in the follicular phase (F), 16 women in the luteal phase (L), and 30 women in the 36th week of gestation (P) using GC–MS. The steroid levels were similar in M and F, increased about thrice in L and escalated in P (38–410 times compared with F). The PICs were prevalent over the PIs (16–150 times). Higher ratios of 5-PIC to 5-PI found in P indicate the more intensive conjugation of 5-PI during pregnancy. This mechanism probably provides for the elimination of neuroinhibitory P3 5 in the maternal compartment. Additionally, our result points to a limited sulfation capacity for neuroinhibitory P3 5ß in P. In contrast to the situation in M, F, and L where the P3 5ß C is the most abundant PIC, and P3 5ß is present in minor quantities compared with the P3 5 , P3 5ß may acquire physiological importance during pregnancy, contributing to the sustaining thereof. On the other hand, the declining formation of P3 5ß may participate in the initiation of parturition, given the relative abundance of the steroid, its potency to suppress the activity of oxytocin-producing cells and its effectiveness in uterine relaxation.