Estradiol and estriol suppress CYP1A expression in rainbow trout primary hepatocytes.
Hepatic levels of the pollutant inducible enzyme, CYP1A, are strongly suppressed in spawning female fish, a phenomenon attributed to high plasma levels of the female sex steroid hormone, estradiol. To evaluate the contribution of estrogen metabolites to estradiol-mediated CYP1A regulation, we treated primary hepatocytes isolated from juvenile rainbow trout (Oncorhynchus mykiss) with vehicle, 17beta-estradiol, or the estrogen metabolite, estriol, alone and in combination with each other and with the potent CYP1A inducer, benzo[a]pyrene (B[a]P). We found dose-dependent suppression of B[a]P-induced CYP1A activity by both steroids relative to controls. At 10(-7) M doses, estradiol and estriol suppressed B[a]P-induced CYP1A activity by 3- and 2-fold, respectively. Although not statistically significant, mean basal CYP1A activity levels were 15- and 13-fold lower in estradiol and estriol treated hepatocytes, respectively, relative to vehicle treated controls. Combining doses of estradiol and estriol failed to produce synergistic suppression of either basal or B[a]P-induced CYP1A activity relative to treatment with either steroid alone. The observed suppression is well below the often strong suppression observed in spawning female fish. We conclude that factors in addition to estradiol and estriol are likely involved in producing sexual dimorphism in CYP1A expression observed in spawning fish.
Elskus
Adria A
AA
Department of Biology, 101 Morgan Building, University of Kentucky, Lexington, KY 40506-0225, USA. aelskus@uky.edu
D000704:Analysis of Variance; D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D004964:Estriol / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000378:metabolism*
D001564:Benzo(a)pyrene; D004958:Estradiol; D019363:Cytochrome P-450 CYP1A1; D004964:Estriol