Estrogen-Binding Sites and Their Functional Capacity in Estrogen Receptor Double Knockout Mouse Brain
| Autor: | G. Roger Askew, Tammy L. Dellovade, Paul J. Shughrue, Istvan Merchenthaler |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class Molecular Sequence Data Hypothalamus Estrogen receptor Biology Mice Endocrinology In vivo Internal medicine medicine Animals Estrogen Receptor beta Amino Acid Sequence Binding site Estrogen binding In Situ Hybridization Brain Chemistry Mice Knockout Binding Sites Base Sequence Reverse Transcriptase Polymerase Chain Reaction Alternative splicing Estrogen Receptor alpha Immunohistochemistry Mice Inbred C57BL Receptors Estrogen Estrogen RNA splicing Autoradiography Female |
| Zdroj: | Endocrinology. 143:1643-1650 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | Early studies found estrogen-binding sites in the ER knockout (ERalphaKO) mouse brain, suggesting a splice variant of ERalpha or another ER. The discovery of ERbeta suggested that binding was due to ERbeta, although questions about an ERgamma remained. To test this hypothesis, ERbetaKO mice were generated and crossed with ERalphaKO mice, and ERalpha/betaKO animals were used for in vivo binding studies with [(125)I]estrogen. The results revealed nuclear binding sites in the ERalpha/betaKO hypothalamus and amygdala. As the binding resembled the distribution of ERalpha, we evaluated the presence of ERalpha splicing variants. A nonphysiological splice variant of ERalpha was identified in ERalpha/betaKO brain and uterus, but was absent in wild-type mice. ERalpha immunoreactivity was also detected in regions of ERalpha/betaKO brain where residual binding was seen. To ascertain the functionality of the variant, the regulation of PR was assessed in brain. The results revealed that E2 significantly increased PR expression, an indication that the variant can regulate gene transcription. These data demonstrate the presence and functionality of an ERalpha variant in ERalpha/betaKO brain and suggest that the residual binding and regulation of PR in ERalpha/betaKO brain can be accounted for by the variant. |
| Databáze: | OpenAIRE |
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