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5 alpha-Reductase activity in human placenta.

L Milewich, N F Gant, B E Schwarz

    American Journal of Obstetrics and Gynecology
    |March 15, 1979
    PubMed
    Summary
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    Pregnant women have higher levels of 5 alpha-pregnane-3,20-dione. Placental tissue in vitro synthesizes this steroid from progesterone, with optimal production at pH 8.8, indicating a key role in pregnancy.

    Area of Science:

    • Steroid metabolism
    • Reproductive endocrinology
    • Biochemistry

    Background:

    • 5 alpha-pregnane-3,20-dione is elevated in pregnant women compared to non-pregnant women during the luteal phase.
    • Understanding the synthesis and role of progesterone metabolites during pregnancy is crucial.

    Purpose of the Study:

    • To investigate the in vitro synthesis of 5 alpha-reduced pregnanes from progesterone by human placental tissue.
    • To characterize the metabolites produced and determine the optimal conditions for their formation.

    Main Methods:

    • Incubation of placental tissue minces and homogenates with [3H]progesterone in the presence of nicotinamide-adenine dinucleotide phosphate.
    • Isolation and characterization of metabolites using chromatography, derivative formation, and crystallization with radiolabeled standards.

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  • Determination of pH optimum and measurement of synthesis rates.

    • Main Results:

    • Human placental tissue synthesized [3H]5 alpha-pregnane-3,20-dione and [3H]3 beta-hydroxy-5 alpha-pregnan-20-one from [3H]progesterone.
    • The apparent pH optimum for 5 alpha-pregnane-3,20-dione synthesis was 8.8.
    • No 5 beta-reduced pregnanes were detected. Synthesis rates ranged from 109 to 197 pmoles/gm/hr at pH 7.4.

    Conclusions:

    • The human placenta actively synthesizes 5 alpha-reduced progesterone metabolites in vitro.
    • This synthesis occurs optimally at a slightly alkaline pH, suggesting a specific enzymatic pathway.
    • The placenta does not appear to produce 5 beta-reduced metabolites from progesterone.