Interaction between Dioxin Signaling and Sex Steroid Hormones

Abstract

Dioxin,2,3,7,, is an environmental contaminant that produces potent toxic effects in humans and animals. TCDD is carcinogenic at multiorgan sites and induces disorders of reproduction, development, and immunity. It has been considered that the effects of TCDD partly involve disruption of the endocrine system, since TCDD causes progressive endometriosis in the rhesus monkey, suppresses development of the male reproductive system and sexual dimorphism of the brain, and damages the ovaries. These effects suggest alteration of sex steroidogenesis in the target organs. To clarify the endocrine disruptive action of TCDD, many studies of its effects on estrogen-responsive cell lines have been conducted. This mini-review describes recent experiments conducted in the authors' laboratory and discusses our understanding of the molecular mechanisms of interaction between dioxin signaling and sex-steroid hormones, focusing on three issues: 1) influence of estrogen on TCDD-induced cytochrome P4501A1 (CYP1A1) protein in vivo; 2) influence of estrogen on TCDD-induced xenobiotic response element (XRE) transactivation in cultured cell systems; and 3) effect of hormone-receptor status on TCDD-induced XRE transactivation and its relation to the cell cycle.

Molecular interactions of the aryl hydrocarbon receptor and its biological and toxicological relevance for reproduction

“…In ECC-1 endometrial carcinoma cells exposed to TCDD, Ricci et al (1999) also described an AhR-mediated reduction in ERalpha protein and ER-alpha-mediated transcriptional activity. By contrast, TCDD-activated AhR did not reduce ER-alpha protein in the endometrial carcinoma cells KLE AhR role in female reproduction 381 and RL95-2, suggesting that proteasomal degradation varies according to the specific cellular background (Sone & Yonemoto 2002). Reduced ER-alpha protein levels have been described for several human endometrial pathologies.…”

Ten Years of Mixing Cocktails: A Review of Combination Effects of Endocrine-Disrupting Chemicals

“…Although not estrogenic themselves, AhR agonists have been reported to suppress some E 2 -induced responses, not by antagonizing hormone binding to the ER but by down-regulation of ER expression, induction of steroid-metabolizing enzyme systems such as CYP 1A1 and 1A2, and inhibiting various growth factors and cell cycle regulators ( Chen et al 2001 , Reen et al 2002 , Safe 1998 ). There is a rich literature about the molecular biology underlying the interactions between dioxins and estrogens ( Sone and Yonemoto 2002 ).…”