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Neuroactive Pregnanolone Isomers during Pregnancy

Antonín Paízek, Martin Hill, Radmila Kancheva, Helena Havlíková, Lyudmila Kancheva, Josef Cindr, Andrea Paková, Vladimír Pouzar, Ivan ern, Pavel Drbohlav, Zdenk Hájek and Luboslav Stárka

Department of Gynecology and Obstetrics, First Medical Faculty, Charles University (A.Pa., A.Pa., P.D., Z.H.); Institute of Endocrinology (M.H., R.K., H.H., L.K., L.S.); Institute of Clinical and Experimental Medicine (J.C.); and Institute of Organic Chemistry and Biochemistry (V.P., I.C.), CZ 128 51 Prague, Czech Republic

Address all correspondence and requests for reprints to: Dr. Martin Hill, Institute of Endocrinology, Národní Tída 8, CZ 116 94 Prague 1, Czech Republic. E-mail: mhill{at}endo.cz.

The pregnanolone isomers (PI) allopregnanolone (3-hydroxy-5-pregnan-20-one), pregnanolone (3-hydroxy-5ß-pregnan-20-one), isopregnanolone (3ß-hydroxy-5-pregnan-20-one), epipregnanolone (3ß-hydroxy-5ß-pregnan-20-one), progesterone, and estradiol were measured in 138 pregnant women. The sampling was carried out from the first through the 10th month of pregnancy. Gas chromatography-mass spectrometry analysis and RIA were used for the measurement of steroid levels. The ratios of individual PI were similar to those found previously around parturition: about 25:10:7:1 for allopregnanolone, pregnanolone, isopregnanolone, and epipregnanolone, respectively. All the PI showed a significant increase during pregnancy, which was more pronounced in the 3-steroids. The results indicated changing ratios between 3- and 3ß-PI and between 5- and 5ß-PI throughout pregnancy. The constant allopregnanolone/isopregnanolone ratio found through pregnancy weakened the hypothesis of the role of isopregnanolone in the onset of parturition. The ratio of estradiol (stimulating uterine activity) to 5-PI and epipregnanolone exhibited significant changes during pregnancy in favor of estradiol up to the sixth or seventh month, in contrast to the constant estradiol/pregnanolone ratio. A pregnancy-stabilizing role of pregnanolone, counterbalancing the stimulating effect of estradiol on the onset of parturition, was suggested.