Cross-Talk in the Female Rat Mammary Gland: Influence of Aryl Hydrocarbon Receptor on Estrogen Receptor Signaling.

Autor:	Helle, Janina1 Janina.Helle@tu-dresden.de, Bader, Manuela I.1, Keiler, Annekathrin M.1, Zierau, Oliver1, Vollmer, Günter1, Chittur, Sridar V.2, Tenniswood, Martin2, Kretzschmar, Georg1
Předmět:	*Animal experimentation Analysis of variance Breast DNA probes Estrogen Immunohistochemistry Rats Research funding Data analysis software Microarray technology Signal peptides Descriptive statistics Fluoroimmunoassay In vitro studies In vivo studies
Zdroj:	Environmental Health Perspectives. May2016, Vol. 124 Issue 5, p601-610. 10p. 6 Graphs.
Abstrakt:	BACKGROUND: Cross-talk between the aryl hydrocarbon receptor (AHR) and the estrogen receptor (ER) plays a major role in signaling processes in female reproductive organs. OBJECTIVES: We investigated the influence of the AHR ligand 3-methylcholanthrene (3-MC) on ER-mediated signaling in mammary gland tissue of ovariectomized (ovx) rats. METHODS: After 14 days of hormonal decline, ovx rats were treated for 3 days with 4 μg/kg 17β-estradiol (E2), 15 mg/kg 8-prenylnaringenin (8-PN), 15 mg/kg 3-MC, or a combination of these compounds (E2 + 3-MC, 8-PN + 3-MC). Whole-mount preparations of the mammary gland were used to count terminal end buds (TEBs). Protein expression studies (immunohistochemistry, immunofluorescence), a cDNA microarray, pathway analyses, and quantitative real-time polymerase chain reaction (qPCR) were performed to evaluate the interaction between AHR- and ER-mediated signaling pathways. RESULTS: E2 treatment increased the number of TEBs and the levels of Ki-67 protein and progesterone receptor (PR); this treatment also changed the expression of 325 genes by more than 1.5-fold. Although 3-MC treatment alone had marginal impact on gene or protein expression, when rats were co-treated with 3-MC and E2, 3-MC strongly inhibited E2-induced TEB development, protein synthesis, and the expression of nearly half of E2-induced genes. This inhibitory effect of 3-MC was partially mirrored when 8-PN was used as an ER ligand. The anti-estrogenicity of ligand-activated AHR was at least partly due to decreased protein levels of ERα in ductal epithelial cells. CONCLUSION: Our data show transcriptome-wide anti-estrogenic properties of ligand-activated AHR on ER-mediated processes in the mammary gland, thereby contributing an explanation for the chemopreventive and endocrine-disrupting potential of AHR ligands. [ABSTRACT FROM AUTHOR]
Databáze:	GreenFILE
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