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J.Health Sci., 48(5), 385-392, 2002
-Minireview-
Interaction between Dioxin Signaling and Sex Steroid Hormones
Hideko Sone* and Junzo Yonemoto
Health Effects Research Team, Endocrine Disruptors and Dioxin Research Project, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan
Dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 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.
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