Uptake and distribution of glucocorticoids in cell nuclei of rat heart in cell-free system: Dependence on concentrations and forms of added hormones
| Autor: | L.A. Medvedeva, Yu.M. Seleznev, N.G. Volkova, Sergei M. Danilov, Vladimir N. Smirnov |
|---|---|
| Rok vydání: | 1979 |
| Předmět: |
Male
Receptors Steroid Peptide hormone Dexamethasone Cytosol Receptors Glucocorticoid Blood serum Glucocorticoid receptor Transcortin medicine Animals Molecular Biology Cell Nucleus Cell-Free System biology Myocardium Rats Biochemistry Cytoplasm biology.protein Carrier Proteins Corticosterone Cardiology and Cardiovascular Medicine Glucocorticoid Hormone medicine.drug |
| Zdroj: | Journal of Molecular and Cellular Cardiology. 11:289-302 |
| ISSN: | 0022-2828 |
| DOI: | 10.1016/0022-2828(79)90442-5 |
| Popis: | Accumulation by rat heart cell nuclei in vitro of free and protein-bound [3H]corticosterone and [3H]dexamethasone was investigated. [3H]Glucocorticoid-protein complexes were prepared by incubation of labelled hormones with diluted blood serum and cytosol containing glucocorticoid cytoreceptor, transcortin-like protein and various amounts of transcortin. At concentrations of 2 × 10−9 to 25 × 10−9 m binding to cytoreceptor enhances nuclear accumulations of hormones. Uptake of [3H]corticosterone depends on the ratio of binding proteins present in cytosol. The higher the part of glucocorticoid bound to cytoreceptor the larger the amounts accumulated in nuclear fractions. At relatively high concentrations (5 × 10−8 m and higher) nuclei readily accumulate transcortin-bound and free forms of [3H]corticosterone and binding to transcortin evidently facilitates nuclear uptake. Studies with Triton X-100 and KCl extractions of incorporated [3H]glucocorticoids reveal heterogenity of the accumulation process. This process includes uptake of glucocorticoids by outer nuclear membrane as well as intranuclear accumulation. Binding to proteins facilitates in certain conditions uptake of hormones by nuclear membrane. 0.4 m KCl treatment of nuclei incubated with [3H]glucocorticoid-cytosol complex leads to extraction of essential amounts of intranuclear [3H]glucocorticoid fraction a part of which represents macromolecular complexes of hormones. KCl extracts from nuclei incubated with free of transcortin-bound steroid contain a comparatively low percentage of hormone, the greater part of which is present in free form. The data obtained clearly show that at physiological and pharmacological concentrations of hormones the cell nucleus is the target for glucocorticoid action. At the same time the mechanisms of hormonal action on the nucleus at different concentrations is different. At physiological levels of hormones cytoplasmic glucocorticoid receptor plays a key role in the formation of nuclear response to glucocorticoids whereas at pharmacological concentrations some other additional factors connected with the uptake by nucleus of free steroids from cytoplasm as well as extranuclear events can be of value. |
| Databáze: | OpenAIRE |
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