DDE-Induced Changes in Aromatase Activity in Endometrial Stromal Cells in Culture

Abstract

Environmental toxicants are thought to play a role in several estrogen-dependent diseases including breast cancer and endometriosis. Toxicant-induced increased aromatase activity, an enzyme complex that catalyzes the final rate-limiting step in the conversion of androgens to estrogens, has been reported in assays using placental microsomes and cancer cells in vitro. These data suggest that environmental toxicants can increase aromatase activity and thus increase local tissue estrogen levels, which could have implications for estrogen- dependent functions in target tissues. The objective of this study was therefore to quantify the effect of the stable breakdown product of DDT, 2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), a toxicant broadly detected in human adipose tissue, serum and follicular fluid, on aromatase activity in the endometrium, an estrogen-sensitive target tissue. Specifically, the effect of increasing log concentrations of p,p'-DDE on aromatase activity was determined in cultures of endometrial stromal cells (ESC). Relative to controls p,p'-DDE treatment significantly increased aromatase activity in ESC (135%). Moreover, ESC cells treated with p,p'-DDE were immunopositive for aromatase, whereas no aromatase staining could be demonstrated in control cultures. Our data demonstrate that p,p'-DDE treatment can increase aromatase activity in ESC in culture.