The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the hepatic estrogen and glucocorticoid receptors in congenic strains of Ah responsive and Ah nonresponsive C57BL/6J mice
| Autor: | F.H. Lin, George W. Lucier, S.J. Stohs, Joyce A. Goldstein, Linda S. Birnbaum, George C. Clark |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
medicine.medical_specialty
Polychlorinated Dibenzodioxins medicine.drug_class Ratón Receptors Drug Congenic Estrogen receptor Biology Toxicology Mice Receptors Glucocorticoid Glucocorticoid receptor Tyrosine aminotransferase Internal medicine medicine Animals Receptor Tyrosine Transaminase Pharmacology Dose-Response Relationship Drug Mice Inbred C57BL Endocrinology Liver Receptors Aryl Hydrocarbon Receptors Estrogen Estrogen Corticosterone Glucocorticoid medicine.drug |
| Zdroj: | Toxicology and Applied Pharmacology. 108:129-139 |
| ISSN: | 0041-008X |
| Popis: | The present study examines the role of the Ah receptor in the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the binding capacity of the hepatic glucocorticoid (GC) and estrogen (E) receptors in female congenic C57BL/6J mice differing only at the Ah (aromatic hydrocarbon responsiveness) locus. The Ah locus is thought to encode the Ah receptor, which regulates the effects of TCDD and related compounds on cytochrome P450IA1 and appears to mediate most of the toxic effects of TCDD. The differences between Ah responsive (Ahb/b) and nonresponsive (Ahd/d) mice appear to reflect differences in the affinity of the Ah receptor in the two strains for ligands such as TCDD. Administration of a single oral dose of TCDD (30 micrograms/kg) to Ahb/b mice produced approximately a 30% decrease in the maximum binding capacities of both the hepatic GC and E receptors, as well as 50-fold induction of a P450IA1-mediated enzymatic activity, ethoxyresorufin-O-deethylase (EROD). Tyrosine aminotransferase (TAT) activity, which is mediated by the GC receptor, was also decreased approximately 30% by TCDD. Dose-response curves indicated that Ah responsive mice are 10-fold more sensitive to induction of EROD than Ah nonresponsive mice (ED50 1.6 vs 15 micrograms/kg), as would be expected for an effect mediated by the Ah receptor. Dose-response curves also indicated that there was a statistical difference in the responsiveness of the hepatic E receptor to TCDD in the two congenic strains of mice (p less than 0.01). Surprisingly, no significant differences in the dose-response curves for the effect of TCDD on hepatic GC receptor binding or TAT activity were observed in the two strains of mice in two separate experiments. These results indicate that the Ah receptor regulates the effects of TCDD on the binding of estrogen to the hepatic estrogen receptor, but suggest that the decrease in the binding capacity of the hepatic GC receptor does not appear to be mediated directly by the Ah locus. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|