The development of drug-metabolizing enzymes in female sheep livers

The purpose of this investigation was to determine age-related changes of some hepatic drug-metabolizing activities in Lacaune ewes in the foetal, neonatal (1 and 4 weeks), growing (7 months), pregnant (11 months) and adult (6 years) stages. Although microsomal cytochrome P-450 was not detected in 3-month-old foetuses, it increased regularly from 1-week- to 11-month-old animals. Among mixed-function oxidases, the development of aminopyrine and ethylmorphine N-demethylases, benzo(alpha)pyrene hydroxylase and ethoxycoumarin O-deethylase were correlated to that of total cytochrome P-450. Due to their presence in foetal liver or their more rapid evolution, cytochrome b5, NADPH cytochrome c reductase, aniline hydroxylase, benzphetamine N-demethylase and erythromycin N-demethylase did not parallel the ontogenesis of cytochrome P-450. Hepatic transferases showed different developmental patterns from mono-oxygenases, so UDP glucuronyltransferase was detected in the foetus, reached maximum activity in all young ages up to the pregnant stage and subsequently fell in adult ewes. Concerning glutathione S-transferase accepting 1-chloro-2,4-dinitrobenzene as substrate, similar values were obtained in the foetus and all young animals, whereas five- to tenfold higher values were obtained in both pregnant and adult female sheep. N-acetyltransferase using sulphamethazine did not significantly change from foetuses to adults but there were large differences in the capacity of hepatic acetylation between animals belonging to the same group.