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[Experimental data on estradiol 3,17-diethers (author's transl)].

J P Tresca, G Ponsard, D Pigne

    Annales D'Endocrinologie
    |January 1, 1977
    PubMed
    Summary

    Estradiol ethers are biologically active in rats, with activity decreasing with longer side chains. Percutaneous administration of promestriene leads to estradiol formation in the liver, showing antagonist activity against androgens.

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    Area of Science:

    • Endocrinology
    • Pharmacology

    Background:

    • Estradiol ethers exhibit biological activity in female rats.
    • Activity is influenced by the length of the side chain at position 3.
    • Percutaneous administration shows significantly higher activity than subcutaneous injections.

    Purpose of the Study:

    • To investigate the biological activity and metabolic fate of estradiol ethers, specifically promestriene.
    • To determine if de-etherification to estradiol occurs after administration.
    • To assess the antagonist activity of promestriene on androgen-stimulated effects.

    Main Methods:

    • Administration of tritiated promestriene and estradiol to female rats.
    • Comparison of uterine uptake and uterotrophic effects.
    • Analysis of radioactivity in tissues.

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  • Perfused liver experiments to study de-etherification.
  • In vitro and in vivo assessment of 5-alpha-reductase activity.

    • Main Results:

    • De-etherification of both ether groups of promestriene to estradiol was confirmed.
    • Estradiol formation occurs primarily in the liver.
    • Promestriene demonstrated antagonist activity in androgen-stimulated rat models and on 5-alpha-reductase activity.

    Conclusions:

    • Promestriene is a prodrug that is metabolized to estradiol in the liver.
    • The observed biological activity of estradiol ethers is likely due to their conversion to estradiol.
    • Promestriene possesses anti-androgenic properties, acting as an antagonist to androgenic effects.