Dose dependent effects of ethinyloestradiol, diethylstilboestrol and oestradiol on the metabolism of 4 androstene 3,17 dione in rat liver microsomes

K. Einarsson, J. A. Gustafsson, J. E. Sjovall andZietz

    Research output: Contribution to journalArticlepeer-review

    12 Scopus citations

    Abstract

    The effects of administration of ethinyloestradiol (EtE2), 0.1, 0.5 or 1 μg per day, diethylstilboestrol, 5, 100 or 500 μg per day, and oestradiol, 1 or 100 μg per day, for 12 days, on the hepatic microsomal metabolism of 4 [4 14C]androstene 3,17 dione were studied in castrated male and female rats. When rats were given EtE2 in daily doses of 0.1 and 0.5 μg, the activities of the 3α and 17β hydroxysteroid oxidoreductases increased in both male and female rats. A similar tendency was noted for the 5α reductase in female rats. On the other hand, the activities of the 3β hydroxysteroid oxidoreductase and 7α hydroxylase enzyme systems were suppressed in both male and female rats already after administration of 0.1 μg of EtE2. Diethylstilboestrol, administered in doses of 100 and 500 μg, and oestradiol, given in a dose of 100 μg, suppressed the microsomal enzyme activities whereas the lower doses of 5 μg of diethylstilboestrol and 1 μg of oestradiol were without effects. The results indicate that oestrogenic compounds given in doses higher than the physiological one have a suppressing effect on microsomal steroid metabolizing enzyme activities. Ethinyloestradiol has a stimulating effect on certain microsomal enzyme activities and an inhibiting effect on others when administered in an amount of 0.5 μg/kg-1 per day. The findings are discussed in relation to recent reports on impaired drug metabolism in women taking contraceptives.

    Original languageEnglish (US)
    Pages (from-to)54-64
    Number of pages11
    JournalActa endocrinologica
    Volume78
    Issue number1
    DOIs
    StatePublished - 1975

    ASJC Scopus subject areas

    • Endocrinology

    Fingerprint

    Dive into the research topics of 'Dose dependent effects of ethinyloestradiol, diethylstilboestrol and oestradiol on the metabolism of 4 androstene 3,17 dione in rat liver microsomes'. Together they form a unique fingerprint.

    Cite this