Estrogenic and anti-estrogenic influences in cultured brown trout hepatocytes: Focus on the expression of some estrogen and peroxisomal related genes and linked phenotypic anchors
| Autor: | Célia Lopes, Ivone Pinheiro, Ralph Urbatzka, Tânia Vieira Madureira, Fernanda Malhão, Nádia S. Ferreira, Eduardo Rocha, L. Filipe C. Castro |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Trout Health Toxicology and Mutagenesis Peroxisome proliferator-activated receptor Estrogen receptor 010501 environmental sciences Aquatic Science Biology Ethinyl Estradiol 01 natural sciences Vitellogenins 03 medical and health sciences Vitellogenin Internal medicine Peroxisomes medicine Animals Receptor Fulvestrant 030304 developmental biology 0105 earth and related environmental sciences chemistry.chemical_classification 0303 health sciences Estradiol Endoplasmic reticulum Estrogen Receptor alpha Estrogens Peroxisome Cell biology Endocrinology Gene Expression Regulation Receptors Estrogen Nuclear receptor chemistry Hepatocytes biology.protein Estrogen Receptor Antagonists Estrogen receptor alpha Water Pollutants Chemical Signal Transduction |
| Zdroj: | Aquatic Toxicology |
| ISSN: | 0166-445X |
| Popis: | Estrogens, estrogenic mimics and anti-estrogenic compounds are known to target estrogen receptors (ER) that can modulate other nuclear receptor signaling pathways, such as those controlled by the peroxisome proliferator-activated receptor (PPAR), and alter organelle (inc. peroxisome) morphodynamics. By using primary isolated brown trout (Salmo trutta f. fario) hepatocytes after 72 and 96h of exposure we evaluated some effects in selected molecular targets and in peroxisomal morphological features caused by: (1) an ER agonist (ethinylestradiol-EE2) at 1, 10 and 50μM; (2) an ER antagonist (ICI 182,780) at 10 and 50μM; and (3) mixtures of both (Mix I-10μM EE2 and 50μM ICI; Mix II-1μM EE2 and 10μM ICI and Mix III-1μM EE2 and 50μM ICI). The mRNA levels of the estrogenic targets (ERα, ERβ-1 and vitellogenin A-VtgA) and the peroxisome structure/function related genes (catalase, urate oxidase-Uox, 17β-hydroxysteroid dehydrogenase 4-17β-HSD4, peroxin 11α-Pex11α and PPARα) were analyzed by real-time polymerase chain reaction (RT-PCR). Stereology combined with catalase immunofluorescence revealed a significant reduction in peroxisome volume densities at 50μM of EE2 exposure. Concomitantly, at the same concentration, electron microscopy showed smaller peroxisome profiles, exacerbated proliferation of rough endoplasmic reticulum, and a generalized cytoplasmic vacuolization of hepatocytes. Catalase and Uox mRNA levels decreased in all estrogenic stimuli conditions. VtgA and ERα mRNA increased after all EE2 treatments, while ERβ-1 had an inverse pattern. The EE2 action was reversed by ICI 182,780 in a concentration-dependent manner, for VtgA, ERα and Uox. Overall, our data show the great value of primary brown trout hepatocytes to study the effects of estrogenic/anti-estrogenic inputs in peroxisome kinetics and in ER and PPARα signaling, backing the still open hypothesis of crosstalk interactions between these pathways and calling for more mechanistic experiments. |
| Databáze: | OpenAIRE |
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