Biosynthesis of active oestrogens in the breast

Abstract

SynopsisIt is generally accepted that sex hormones play a role in the development of mammary cancer and it is a reasonable assumption that tissue concentration of oestrogens and their androgen precursors, as well as the activity of oestrogen synthetising or metabolising enzymes, may be valuable parameters of hormone dependency. Except for the sulphate conjugates and for testosterone, androgen and oestrogen levels are higher in mammary tissue (ng/g) than in plasma (ng/ml) and as distinct from plasma, tissue oestradiol (the active oestrogen) levels are higher than oestrone levels. Moreover, oestradiol levels are higher in oestrogen-receptor-positive tissues.Sex hormone levels in mammary tissue find their origin in uptake from plasma and in local synthesis. It is unlikely that local aromatase activity accounts for a large fraction of tissue oestrogens but sulphatase activity may be an important determinant of tissue oestrogen concentration. The major precursors of tissue oestrogens are androstenedione and oestrone sulphate respectively, yielding oestrone which is transformed by the 17β-hydroxysteroid dehydrogenase to oestradiol. However, the reverse reaction, conversion of E2 into E1, is much more active and is inversely correlated to dehydroepiandrosterone (sulphate) concentration, which inhibits non-competitively the conversion of E2 into E1. This E2DH activity is higher in E2R positive tumours, suggesting that E2DH is a good marker of hormone dependency. As to prognostic factors, a follow-up study concerning sixty-two postmenopausal women, with a follow up of at least four years, revealed that in the recurrence group (n = 17 ), besides E2R and PgR concentrations, all hormone concentrations as well as E2DH activity were also lower than in the disease-free group.