Common classification schemes for PCB congeners and the gene expression of CYP17, CYP19, ESR1 and ESR2

Abstract

Background: Reliable techniques to measure polychlorinated biphenyl (PCB) congeners make the clearer definition of their effects on human health possible. Given that PCBs are classified as endocrine disrupters, we sought to explore the expression of some key genes involved in sex steroid metabolism.

Objectives: To examine common classification schemes of PCB congeners and determine whether exposure to groups classified by mechanism of action alter the gene expression (GE) of CYP17, CYP19, and ESR1 and ESR2.

Methods: GE and exposure to various classifications of lipid-adjusted PCB congeners were examined in 139 daughters of the Michigan Fisheaters' Cohort. Using mixed models analyses and adjusting for age, menopausal status, and current use of oral contraceptives and hormone replacement therapy, GE data were regressed on exposure to PCB congener groupings based on mechanism of action.

Results: Three novel findings are elucidated: first, that up-regulation of CYP19 expression is associated with exposure to PCB groupings containing dioxin-like, potentially anti-estrogenic, immunotoxic congeners, including PCB IUPAC #74, #105, #118, #138, #156, #157, #158, #167, and #170 from this cohort. Second, that exposure to similar congeners (PCB IUPAC #105, #156, #157, #158, and #167 in this cohort) but using a classification based solely on hormonal mechanisms of action is associated with increased expression of ESR2. Third, that increased expression of CYP17 is of borderline significance when associated with exposure to PCB IUPAC #118, #138, and #156.

Conclusions: These findings are both counter-intuitive and intriguing. Rather than exhibiting anti-estrogenic effects alone, they suggest that these congeners up-regulate the major enzyme involved in estrogen synthesis and tend to confirm previous findings of links between AhR and ER signaling pathways. Replication of these findings, expansion of the number of genes examined, exploration of mixtures of environmental chemicals, and subsequent study of health outcomes in a larger cohort are future priorities.