Effect of hormone manipulation on oxidation, reduction and sulphurylation of dehydroepiandrosterone and oestrone in DMBA-induced rat mammary tumours.

Using the DMBA-induced mammary tumour as a model, the effect of hormone manipulation on steroid sulphurylation and on oxidative and reductive metabolism has been investigated. Oestradiol-17 beta, or oestradiol-17 beta + progesterone, administered to oophorectomized animals, had no effect on adenosine-3'-phosphate-5'-phosphosulphate formation in the tumours. Dehydroepiandrosterone sulphotransferase was also unaffected. A large increase in oestrogen sulphotransferase following administration of oestrogen + progesterone was observed in some but not all tumours, and the overall results were not statically significant. The major metabolities of dehydroepiandrosterone, by both human and carcinogen-induced rat mammary tumours in vitro, are 7-oxygenated derivatives. Oestrogen administration led to a significantly decreased production of total 7-oxygenated derivatives of dehydroepiandrosterone. Conversion to 5-androstene-3 beta, 17 beta-diol was unaffected by the hormones. The rate of formation of oestradiol-17 beta from oestrone was increased 5-fold in growing tumours from animals receiving oestrogen, or oestrogen + progesterone, compared to regressing tumours in oophorectomized control animals.