Steroid dynamics in the normal and carcinomatous mammary gland

Abstract

As an approach to the study of the origin of estrogens in breast cancer tissue, the concentration of estrogens and their androgen precursors, as well as aromatase and 17β-dehydrogenase activities in normal glandular (GL) and cancerous (CA) breast tissue were determined and correlations with plasma levels and/or receptor status were studied. In both normal GL and CA breast tissue, steroid concentrations were significantly higher than plasma conc., except for dehydroepiandrosterone sulphate (DHEAS), estrone sulphate (E 1S) and testosterone (T). Androgen conc. were lower, but estrogen conc. were higher in CA than in GL breast tissue. Estradiol (E 2) conc. was positively correlated with the E 2R conc. mean E 2 conc. corresponcling to an estimated E 2R occupancy of about 25%. Aromatase and 17β-hydroxysteroid dehydrogenase (E 2DH) (E 2→ E 1) activities were observed in all breast CA and GL tissues, aromatase accounting probably only for a small fraction of tissue estrogens. E 2DH, but not aromatase activity, was significantly higher in E 2R+ than in E 2R— tissues and was negatively correlated with tissue dehydroepiandrosterone (DHEA) and DHEAS conc.; the latter two steroids are non competitive inhibitors of E 2DH which inactivates E 2 to E 1. Conclusion : in both normal and carcinomatous breast tissue, conc. of E 1 and E 2 are significantly higher than in plasma, suggesting either uptake or local synthesis. As to the latter, aromatase activity accounts probably only for a minor fraction of the tissue estrogens. Breast CA tissue has higher aromatase and E 2DH activity than normal glandular tissue, E 2 conc. and E 2DH activity being higher in E 2R+ hormone sensitive, tumors than in E 2R-tumors. Tissue conc. of DHEA(S) which inhibits oxidative inactivation of E 2, is negatively correlated with E 2DH activity and may have an important modulating role in intratissular estrogen metabolism.