Oxidative metabolism of estrogens

This project was undertaken to obtain more information about the nature of the water-soluble metabolites formed by rat liver since these had been shown to differ from the normal conjugates found in other species and are influenced by the sex of the animal and also by compounds in the soluble fraction of the cell. A comparison was made between these products and those formed from estrogens by mushroom phenolase under similar conditions, and it was found that glutathione had the same effect as the soluble fraction of the cell in increasing the yield of water-soluble metabolites in the rat liver microsomal system. This tripeptide also competed effectively with protein-binding and proposals to account for this reaction have been put forward. A marked increase in the yield of water-soluble estrogen derivatives was also observed when glutathione was added to the phenolase system, and although a different mechanism may be involved, similar types of products were formed. A competitive reaction for protein-binding in the presence of glutathione was again demonstrated. Sulphydryl compounds such as cysteine, ergothionine, homocysteine and thiolhistidine had little or no effect in either of the two systems, and the reaction therefore appears to be specific for glutathione. Oxidized glutathione was ineffective in increasing the yield of water-soluble metabolites indicating that the sulphydryl group was involved, and N-ethylmaleimide was found to be strongly inhibitory. The effect of estrogen oxidation products on the in vitro inactivation of gonadotropins was also investigated.Medicine, Faculty ofBiochemistry and Molecular Biology, Department ofGraduat