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• W2045934057 endingPage "457" @default.
• W2045934057 startingPage "443" @default.
• W2045934057 abstract "The metabolism and production rates of 3α-hydroxy-5α-pregnan-20-one sulfate and the 3-sulfate and 3,20-disulfate of 5α-pregnane-3α,20α-diol in pregnant women were studied. The steroid sulfates were labeled with deuterium in the 3β,11,11- or 3β,11,11,20β-positions and were injected intravenously. The deuterium content of steroids in the monosulfate and disulfate fraction of plasma collected at different times after the injection was determined by capillary column gas chromatography/mass spectrometry. The injected steroid sulfates underwent oxidoreduction at C-20 and 16α-hydroxylation. In addition, the 3-sulfate of5α-pregnane-3α,20α-diol became hydroxylated at C-21. The pregnanediol andpregnanetriol monosulfates were also converted to disulfates. No evidence was obtained for a metabolic sequence involving hydrolysis, oxidoreduction, and resulfation at the C-3 position. Production rates and rates of metabolic transformations were determined using different one- and two-pool models. The production rate of the pregnanolone / pregnanediol monosulfate couple was 0.08 to 0.5 mmol/24 h, the variability probably depending both on individual factors and stage of pregnancy. The half-life time for oxidation and reduction at C-20 was 0.1 to 0.4 hours, reduction being the faster process. The half-life time for the turnover of the steroid skeleton was 1.3 to 3.3 hours. The injected steroid monosulfates were 16α-hydroxylated at a rate of 1 to 8 μmol/24 h. A significant fraction of these 16α-hydroxylated steroid sulfates, 0.5 to 25 μmol 124 h, was formed from other, probably unconjugated, precursors. The 16α-hydroxylated steroid monosulfates underwent rapid oxidoreduction at C-20. The 3-sulfate of 5α-pregnane-3α,20α-diol was hydroxylated at C-21. The production rate of 5α-pregnane-3α,20α,21-triol 3-sulfate was 8 to 36 μmol 124 h in four women and 180 μmol/24 h in one woman, and this steroid was not formed from other precursors to a significant extent. 5α-Pregnane-3α,20α-diol disulfate was a metabolic end product accounting for a major part of the elimination of the steroids injected. Its half-life time was 1.4 to 2.8 hours. The results show that the formation of sulfated steroids with a 3α-hydroxy-5α configuration may account for 50% of the metabolism of progesterone in late pregnancy. (Steroids 55:443–457, 19%)" @default.
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• W2045934057 date "1990-10-01" @default.
• W2045934057 modified "2023-09-30" @default.
• W2045934057 title "Stable isotope studies on steroid metabolism and kinetics: sulfates of 3α-hydroxy-5α-pregnane derivatives in human pregnancy" @default.
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• W2045934057 doi "https://doi.org/10.1016/0039-128x(90)90013-2" @default.
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