Glucocorticoid receptors in lung. Mechanism of specific glucocorticoid uptake by fetal rabbit lung nuclei.
After exposure of fetal rabbit lungs to glucocorticoid in vivo or in vitro, the hormone binds to specific receptors localized in the cytoplasm and in the nuclei. The present studies are compatible with a mechanism by which the nuclear receptor originates from the cytoplasm and arises from a hormone-, temperature-, and ionic strength-dependent transfer of the cytoplasmic receptor into the nucleus. This conclusion is reached from the following observations. Specific binding of glucocorticoid to nuclei from lungs not previously exposed to the hormone is not observed unless the cytosol is also present. In the presence of cytosol, nuclear uptake of the hormone is very slow at 0 degrees but is highly enhanced with increasing temperature. Concomitantly with the increased nuclear uptake there is an equiivalent loss of glucocortoid-receptor complex from the cytosol, indicating that the complex is transferred to the nuclei by a temperature-dependent process. Although the nuclei do not bind the cytoplasmic complex at 0 degrees, they do so provided that the cytosol is briefly heated in the presence of hormone prior to mixing with the nuclei. Thus the cytoplasmic complex must first be activated before it can bind to nuclei..
D000818:Animals; D001665:Binding Sites; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism*; D005260:Female; D005333:Fetus; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D009994:Osmolar Concentration; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy; D011485:Protein Binding; D011817:Rabbits; D011956:Receptors, Cell Surface; D013347:Subcellular Fractions / Q000378:metabolism; D013696:Temperature; D013997:Time Factors
D011956:Receptors, Cell Surface; D011189:Potassium Chloride; D003907:Dexamethasone