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Related Experiment Videos

Perinatal development of conjugative enzyme systems

G W Lucier

    Environmental Health Perspectives
    |December 1, 1976
    PubMed
    Summary
    This summary is machine-generated.

    Developmental pharmacology reveals shifts in glucuronidation balance, with deglucuronidation dominating in fetuses and glucuronidation in adults. The toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces drug metabolism enzymes postnatally.

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    Area of Science:

    • Pharmacology
    • Developmental Biology
    • Toxicology

    Background:

    • Studying conjugative enzymes in developmental pharmacology presents unique challenges and priorities.
    • Understanding the balance between glucuronidation and deglucuronidation is crucial for assessing drug metabolism during development.

    Purpose of the Study:

    • To evaluate the relative rates of UDP glucuronyltransferase and beta-glucuronidase during perinatal development.
    • To determine the net balance of glucuronidation/deglucuronidation in hepatic and extrahepatic tissues across developmental stages.
    • To investigate the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on drug-metabolizing enzymes and steroid/non-steroid glucuronidation during development.

    Main Methods:

    • Comparative analysis of UDP glucuronyltransferase and beta-glucuronidase activity in fetal and adult tissues.

    Related Experiment Videos

  • Administration of TCDD during gestation and assessment of its impact on postnatal enzyme activities.
  • Foster mother experiments and tissue distribution studies using TCDD-14C.
  • Enzyme activity assays for p-nitrophenol glucuronyltransferase, benzpyrene hydroxylase, and steroid/diethylstilbestrol (DES) glucuronidation.

    • Main Results:

    • De-glucuronidation predominated in fetal tissues, while glucuronidation was more prominent in adults.
    • TCDD significantly induced postnatal activities of p-nitrophenol glucuronyltransferase and benzpyrene hydroxylase.
    • Postnatal induction by TCDD was primarily mediated by exposure through maternal milk.
    • TCDD induced non-steroid glucuronidation but did not affect the postnatal development of steroid glucuronidation or DES glucuronidation.
    • Fetal distribution of DES and its glucuronide correlated with perinatal steroid glucuronyltransferase activity.

    Conclusions:

    • The balance of glucuronidation shifts from de-glucuronidation in fetuses to glucuronidation in adults.
    • TCDD is a potent inducer of specific drug-metabolizing enzymes, with exposure via milk being a key factor in postnatal induction.
    • Developmental pathways for steroid and non-steroid glucuronidation exhibit differential sensitivity to TCDD exposure.