POSTNATAL AGE: A DETERMINANT IN THE RESPONSIVENESS OF HEPATIC MICROSOMAL MIXED FUNCTION OXIDASE (HMMFO) TO THYROXINE (T4) EFFECT

Abstract

Drug oxidative enzymes are refractory to induction in fetal rats 1 week (wk) prior to term but are readily inducible thereafter, indicating that age influences responsiveness of HMMFO to induction. To test whether postnatal age exerts quantitative and qualitative (induction or inhibition) effects in the response of HMMFO to drugs, T4, known to induce enzyme maturation, was given in equivalent doses of 1 mg/kg/day (d) × 3 d to male rats of varying ages (birth to 10 wks) followed by measurements of the component enzymes of HMMFO and substrate oxidations. Untreated rats of corresponding ages served as controls. The results show varying responses of HMMFO to T4 as a function of age. T4 decreased aminopyrine N-demethylase activity at 1-3 wks, had no effect at 4 wks, and induced at 5-10 wks. Reverse effects were noted with aniline p-hydroxylase, where induction was noted from 3 d to 4 wks followed by inhibition at 5-10 wks. Induction of NADPH oxidase was noted only at ages 3 d and 4 wks. NADPH cytochrome c reductase was highly inducible at all ages except at age 3 wks. Cytochrome P-450 was inhibited at all ages. The data show that the enzyme titres achieved in response to T4 is dependent on age. Where induction is desirable (e.g. of HMMFO, of lung surfactant, of glucuronyl transferase, etc.) the effectiveness of induction may depend on the age at which the inducer is administered.

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