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Estrogen-induced zonal changes in rat liver sinusoids

J P Raufman, D L Miller, J J Gumucio

    Gastroenterology
    |December 1, 1980
    PubMed
    Summary
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    Ethynyl estradiol in oral contraceptives alters rat liver sinusoids, causing zone 1 dilatation and zone 3 constriction. These zonal changes in hepatic sinusoids persist with prolonged exposure.

    Area of Science:

    • Hepatology
    • Pharmacology
    • Toxicology

    Background:

    • Estrogen-containing oral contraceptives are linked to hepatic sinusoid changes.
    • Systematic studies on estrogen-induced sinusoidal alterations are limited.
    • Understanding these changes is crucial for assessing oral contraceptive safety.

    Purpose of the Study:

    • To quantitatively define and locate estrogen-induced changes in hepatic acinar zones.
    • To investigate the impact of ethynyl estradiol on liver sinusoid morphology.
    • To establish a dose-response and time-course for these alterations.

    Main Methods:

    • Morphometric analysis of rat liver sinusoids.
    • Administration of ethynyl estradiol (0.125 mg/100 g body wt) for 2 or 6 weeks.

    Related Experiment Videos

  • Analysis using an automatic image analyzer (Quantimet 720) on glutaraldehyde-fixed liver sections.

    • Main Results:

    • Ethynyl estradiol significantly increased the zone 1/zone 3 sinusoid volume fraction ratio (2.04 vs. 0.87-0.76).
    • This ratio increase resulted from increased zone 1 and decreased zone 3 sinusoid volume fractions.
    • Sinusoid surface-to-volume ratios were altered, indicating changes in solute-wall interaction probability.

    Conclusions:

    • Ethynyl estradiol induces selective zonal changes in rat liver sinusoids.
    • These alterations include persistent dilatation of zone 1 sinusoids and constriction of zone 3 sinusoids.
    • The findings highlight potential hepatic effects of synthetic estrogens found in oral contraceptives.