Isomer-specific activity of dichlorodyphenyltrichloroethane with estrogen receptor in adult and suckling estrogen reporter mice
| Autor: | Giuseppina Ruggeri, Michele Raviscioni, D. Di Lorenzo, Paolo Ciana, Adriana Maggi, Giorgio Biasiotto, Pietro Apostoli, R. Villa, Silvana Belloli, Alberto Albertini |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Aging animal structures medicine.drug_class Estrogen receptor Gene Expression Mice Transgenic Biology Response Elements Thymidine Kinase Gas Chromatography-Mass Spectrometry DDT Basal (phylogenetics) Mice Structure-Activity Relationship Endocrinology Prostate Genes Reporter Internal medicine parasitic diseases medicine Animals Luciferase Luciferases Fulvestrant Lung Estradiol organic chemicals Antagonist Estrogen Antagonists Brain Animals Suckling Kinetics medicine.anatomical_structure Animals Newborn Liver Receptors Estrogen Estrogen Specific activity Receptors Progesterone |
| Zdroj: | Endocrinology. 143(12) |
| ISSN: | 0013-7227 |
| Popis: | We investigated the tissue-specific effects of dichlorodyphenyltrichloroethane (DDT) isomers in adult and suckling newborn mice, using a novel mouse line engineered to express a reporter of estrogen receptor transcriptional activity (ERE-tkLUC mouse). The DDT isomers p,p’-DDT [1,1,1-trichloro2,2-bis(p-chlorophenyl) ethane] and o,p’-DDT [1,1,1-trichloro-2(p-chlorophenyl)-2-(o-chlorophenyl) ethane] were specifically selected as a weak and a strong estrogen, respectively. In adult male mice, p,p’-DDT induced luciferase activity in liver, brain, thymus, and prostate but not in heart and lung. The effect of p,p’-DDT was dose-dependent, maximal at 16 h after sc treatment, and completely blocked by the estrogen receptor antagonist ICI-182,780. In all the organs analyzed, except the liver, administration of o,p’-DDT showed a pattern of luciferase induction superimposable to that of its isomer p,p’-DDT. In liver, o,p’-DDT significantly decreased basal luciferase activity and blocked the reporter induction by 17-estradiol. These data lead us to hypothesize that a modulation of ER activity may be involved in the toxic effects of DDT demonstrated by epidemiological and experimental studies. Luciferase activity was also studied in 4-d-old mice lactating from a mother injected with either p,p’-DDT or o,p’-DDT. Both isomers induced a 2-fold increase in the newborn brain. An opposite effect was observed in liver, where p,p’-DDT increased and o,p’-DDT decreased luciferase, thus indicating that these compounds modulate ER activity in adult and newborn tissues by use of a similar mechanism. The ERE-tkLUC mouse proves to be a suitable tool to functionally assess the tissue specificity of estrogenic/antiestrogenic compounds in adult (as well as in suckling) mice. (Endocrinology 143: 4544 – 4551, 2002) |
| Databáze: | OpenAIRE |
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