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Studies on the decrease of liver cytochrome P-450 content by triiodothyronine.

D L Kleiman de Pisarev1, A M Ferramola de Sancovich, H A Sancovich

  • 1Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Argentina.

Biochimica Et Biophysica Acta
|May 24, 1991
PubMed
Summary
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Triiodothyronine (T3) treatment significantly reduces cytochrome P-450 levels in rat liver microsomes by impacting apocytochrome P-450 levels, not heme synthesis or degradation.

Area of Science:

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Background:

  • Cytochrome P-450 enzymes are crucial for drug metabolism and detoxification.
  • Thyroid hormones, like triiodothyronine (T3), can influence the expression of various liver enzymes.
  • Previous observations indicated a decrease in hepatic microsomal cytochrome P-450 content following T3 administration.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying the reduction of cytochrome P-450 levels induced by T3.
  • To investigate whether T3 affects heme synthesis, heme degradation, or apocytochrome P-450 levels.

Main Methods:

  • Rats were administered triiodothyronine (T3).
  • Microsomal fractions were isolated from rat livers.
  • Enzyme activities related to heme metabolism were assayed.

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  • Heme synthesis precursor incorporation (3H-delta-aminolaevulinate) was measured.
  • Sodium dodecyl sulfate (SDS) gel electrophoresis was used to assess protein levels.

    • Main Results:

    • T3 administration led to a 50% decrease in hepatic microsomal cytochrome P-450 content.
    • Enzymes involved in heme synthesis and degradation showed unaltered activity.
    • Incorporation of 3H-delta-aminolaevulinate into microsomal heme was significantly reduced.
    • SDS-PAGE revealed a decrease in apocytochrome P-450 levels.
    • The binding affinity of apocytochrome P-450 for heme was not found to be limiting.

    Conclusions:

    • The reduction in cytochrome P-450 levels by T3 is primarily due to a decrease in apocytochrome P-450 levels.
    • Thyroid hormone's effect on cytochrome P-450 appears to be mediated at the level of apoprotein synthesis or stability.
    • This suggests that the regulation of apocytochrome P-450 quantity is a key event affected by T3 treatment.