Interactions of Catecholestrogens with Cytoplasmic and Nuclear Estrogen Receptors in Rat Pituitary Gland and Hypothalamus
| Autor: | Rüdiger Ghraf, P. Ball, Elisabeth Hornung, Rudolf Knuppen, Josef Kirchhoff |
|---|---|
| Rok vydání: | 1981 |
| Předmět: |
medicine.medical_specialty
Pituitary gland medicine.medical_treatment Intraperitoneal injection Hypothalamus Estrogen receptor Cytoplasmic receptor Biology Biochemistry Structure-Activity Relationship Cellular and Molecular Neuroscience Cytosol Internal medicine medicine Animals Receptor Cell Nucleus Estradiol Ligand binding assay Estrogens Rats Inbred Strains Estrogens Catechol Rats Kinetics Endocrinology medicine.anatomical_structure Receptors Estrogen Nuclear receptor Pituitary Gland Female |
| Zdroj: | Journal of Neurochemistry. 37:1540-1547 |
| ISSN: | 1471-4159 0022-3042 |
| DOI: | 10.1111/j.1471-4159.1981.tb06325.x |
| Popis: | The affinity of a series of catecholestrogens for 7S cytoplasmic receptor proteins from hypothalamus and pituitary gland of ovariectomised rats was assessed in vitro by a competitive charcoal binding assay at 4°C. The equilibrium dissociation constants (Ki) of catecholestrogens 4-hydroxyestradiol, 4-hydroxyethynylestradiol, 2-hydroxyestradiol, 2-hydroxyethynylestradiol, and 4-hydroxyestrone were of the same order (Ki 0.3–0.6 nm) as those of estradiol and ethynylestradiol (Ki: 0.1 nm). Methylation of 2-hydroxyestradiol led to a substantial loss of binding affinity. Tritium-labelled receptor complexes were demonstrated in KCl extracts of purified nuclei from pituitary and hypothalamic tissue 1 h after intravenous injection of 0.1 mCi tritiated 2- or 4-hydroxyestradiol. These macromolecular complexes sedimented in the 5-6S region of 5–20% (w/v) sucrose gradients containing 0.4 m-KCl. Further evidence for the translocation of estrogen receptors by catecholestrogens into the nuclei of rat pituitary and hypothalamus was the increase in nuclear receptor concentrations, measured by exchange assay, 1 h after the intraperitoneal injection of 0.1 mg unlabelled catecholestrogen. Administration of 4-hydroxyestradiol and 4-hydroxyethynylestradiol increased nuclear receptor concentrations to the same maximal levels as those following application of the same dose of estradiol or ethynylestradiol, whereas the respective 2-hydroxylated compounds exhibited only 60–70% of the maximal translocating capacity. The in vivo translocating capacities of the various catecholestrogens tested at this dose correlated well with their binding affinities for cytosol receptors determined in vitro. |
| Databáze: | OpenAIRE |
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