Relationship between Maternal Progesterones and the Delayed Drug Metabolism in the Neonate

Abstract

The relationship between maternal progesterones and the delayed drug metabolism in the rat neonate was studied with special emphasis on maternal inhibitory substances and their role in the functional development of the endoplasmic reticulum of the neonate. Incubation of liver homogenates and microsomes obtained from fetuses removed by cesarean section 1-3 days before birth indicated the presence of enzymes involved in progesterone metabolism namely 16 alpha- and 6 beta-hydroxylases and delta 4 - 5 alpha-hydrogenase. Enzyme activities determined on liver microsomes of nonpregnant and pregnant rats indicated low 6 beta-hydroxylase activity in both groups and an increase in 5 alpha-hydrogenase in the pregnant when compared to the nonpregnant (p less than . 05 or greater) rats. Weaning 2-week-old rats resulted in an increase in progesterone 16 alpha- and 16 beta-hydroxylase and coumarin 3-hydroxylase activities; however treatment with 5 beta-pregnanediol or 5 beta-pregnanolone prevented these increases. Estradiol or testosterone did not affect these activities. It was concluded that since separation of the neonate from the mother brings about an increase in drug and progesterone hydroxylation it is possible that the low activity of drug metabolizing enzymes of the fetus and neonate is connected with reduced progesterone metabolites originated from the mother.