title: Subunit dissociation as a possible mechanism of glucocorticoid receptor activation.
abstract: For the elucidation of the mechanism of steroid hormone receptor activation, the hydrodynamic properties of the unactivated and activated forms of the nonproteolyzed glucocorticoid receptor from the mouse AtT-20 pituitary tumor cell line were determined. The unactivated, molybdate-stabilized receptor has the following properties: sedimentation coefficient = 9 S; Rs = 8.3 nm; Mr = 317 000; f/f0 = 1.70; axial ratio (prolate ellipsoid) = 14. The activated monomeric receptor has a sedimentation coefficient of 3.2 S, a Stokes radius of 6 nm, a molecular weight of 81 000, a frictional ratio of 1.93, and an axial ratio (prolate ellipsoid) of 18. A receptor species of intermediate size was detected when the analysis was performed in buffer containing both 0.3 M KCl and 20mM Na2MoO4. Its characteristics are as follows: sedimentation coefficient = 5 S; Rs = 8.3 nm; Mr = 176 000; f/f0 = 2.06; axial ratio (prolate ellipsoid) = 22. A preliminary study seemed to indicate that this is an activated form of the receptor. On the basis of the molecular weights, it is likely that the unactivated receptor is a tetramer of identical hormone-binding subunits (Mr = 81 000) while the intermediate form is a homodimer. Alternatively, non-hormone-binding components (receptor-binding factors) may be involved in forming the multimeric, nonactivated receptor complex. In either case, the dissociation of a multimeric, nonactivated receptor into subunits appears to be a possible mechanism of receptor activation. Finally, the addition of high concentrations of 1-thioglycerol promoted activation. Thus, sulfhydryl groups may be involved in receptor subunit interaction.
mesh_terms: D000818:Animals; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008970:Molecular Weight; D009374:Neoplasms, Experimental / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000302:isolation & purification / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*
chemical_list: D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid