Local biosynthesis and metabolism of oestrogens in the human breast.

ABSTRACT

The origin of oestrogens at the level of the breast itself is discussed. In particular in postmenopausal women an accumulation of oestradiol at the site of breast tumours has been documented by a number of independent studies. The mechanism behind the high local oestrogens concentrations is thought to be the in situ production of these steroids by local processes with androstenedione as the main precursor. The presence of all enzymes required for this production has been demonstrated in a large proportion of breast tumours, with probably aromatase, hydroxysteroid dehydrogenase type 1 and sulfatase as the most important enzymes leading to the biologically highly active oestradiol. The individual enzymes that are relevant for the biosynthesis and the metabolism of oestrogens are discussed. The conclusion is reached that a number of these local processes may be involved in the promotion of premalignant lesions and in stimulation of growth of malignant tumours in the human breast.