Figure 1.

Estrogen synthesis in breast tissues. Three enzyme complexes are involved in estrogen synthesis in breast tissues: (1) Aromatase (Arom) which converts androstenedione (A) to estrone (E1); (2) estrone sulfatase (E1-STS) which hydrolyses estrone sulfate (E1-S) to E1 and (3) estradiol-17β-hydroxysteroid dehydrogenase (17β-HSD) Type 1 which reduces E1 to the biologically active estrogen, estradiol (E2). 17β-HSD Type 2 is involved in the inactivation of E2. Higher levels of aromatase activity are detected in stromal fibroblasts. In 'normal' breast tissue, aromatase gene expression is thought to be regulated to a greater extent by promoter (P)I.4 expression, which is stimulated by cytokines such as IL-6 and tumor necrosis factor (TNF)-α. In malignant breast tissues, aromatase gene expression is thought to be regulated to a greater extent by PI.3 and PII, expression of which is stimulated by cAMP and factors such as prostaglandin (PG) E₂, which increase cAMP levels. Cytokines such as IL-6 and TNF-α also increase 17β-HSD Type 1 activity, while their effect on E1-STS activity may be indirect.