Stable isotope studies on steroid metabolism and kinetics: Sulfates of 3 alpha-hydroxy-5 alpha-pregnane derivatives in human pregnancy

Journal Article · Mon Oct 01 04:00:00 EDT 1990 · Steroids; (USA)

DOI:https://doi.org/10.1016/0039-128X(90)90013-2· OSTI ID:5921814

Anderson, R A; Baillie, T A; Axelson, M; Cronholm, T; Sjoevall, K S; Sjoevall, J ^[1]

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1. Karolinska Institutet, Stockholm (Sweden)

The metabolism and production rates of 3 alpha-hydroxy-5 alpha-pregnan-20-one sulfate and the 3-sulfate and 3,20-disulfate of 5 alpha-pregnane-3 alpha,20 alpha-diol in pregnant women were studied. The steroid sulfates were labeled with deuterium in the 3 beta,11,11- or 3 beta,11,11,20 beta-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 16 alpha-hydroxylation. In addition, the 3-sulfate of 5 alpha-pregnane-3 alpha,20 alpha-diol became hydroxylated at C-21. The pregnanediol and pregnanetriol 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 16 alpha-hydroxylated at a rate of 1 to 8 mumol/24 h. A significant fraction of these 16 alpha-hydroxylated steroid sulfates, 0.5 to 25 mumol/24 h, was formed from other, probably unconjugated, precursors. The 16 alpha-hydroxylated steroid monosulfates underwent rapid oxidoreduction at C-20. The 3-sulfate of 5 alpha-pregnane-3 alpha,20 alpha-diol was hydroxylated at C-21.

• OSTI ID: 5921814
• Journal Information: Steroids; (USA), Journal Name: Steroids; (USA) Vol. 55:10; ISSN 0039-128X; ISSN STEDA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BIOLOGICAL HALF-LIFE
CHROMATOGRAPHY
DEUTERIUM
GAS CHROMATOGRAPHY
HYDROGEN ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MAN
MASS SPECTROSCOPY
METABOLISM
METABOLITES
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PREGNANCY
PREGNANES
PRIMATES
SEPARATION PROCESSES
SPECTROSCOPY
STABLE ISOTOPES
STEROIDS
SULFATES
SULFUR COMPOUNDS
TRACER TECHNIQUES
VERTEBRATES