Effect of pregnancy or treatment with cetain steroids on N,N-dimethylaniline demethylation and N-oxidation by rabbit liver or lung microsomes

Abstract

Rates of lung microsomal dimethylaniline (DMA) demethylation and N-oxidation as well as cytochrome P-450 concentrations from 20- and 28-day pregnant rabbits were observed to be as much as 2 times the values measured in lung microsomes from adult female nonpregnant rabbits. These increases were not seen in lung microsomes from 10-day pregnant rabbits, and only small increases were observed in lung microsomes from 15-day pregnant rabbits. In contrast, no differences were seen in hepatic microsomal DMA demethylase or N-oxidase activities at any stage of pregnancy. An attempt was made to correlate high plasma concentrations of steroids during pregnancy with the elevated enzyme activities observed in lung microsomes. Adult nonpregnant rabbits were treated with a variety of steroids, the concentrations of which have been shown to increase in plasma during late pregnancy. No effect on lung or liver microsomal DMA metabolism was observed when rabbits were treated with testosterone propionate. However, after animal pretreatment with the glucocorticoids, dexamethasone and hydrocortisone, there was a 40-60% increase in DMA demethylase and N-oxidase activities in liver and lung microsomes from adult male and nonpregnant female rabbits. Following pretreatment of adult female nonpregnant rabbits with the mineralocorticoid, deoxycorticosterone, an increase of 50% in rats of microsomal DMA metabolism in lung but not in liver was observed.