Subunit dissociation as a possible mechanism of glucocorticoid receptor activation

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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; MW = 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 MW 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 20 mM Na2MoO4. Its characteristics are as follows: sedimentation coefficient = 5 S; Rs = 8.3 nm; MW = 176,000; f/f0 = 2.06; axial ratio (prolate ellipsoid) = 22. Evidently, this is an activated form of the receptor. On the basis of the MW, it is likely that the unactivated receptor is a tetramer of identical hormone-binding subunits (MW = 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 sub-units appears to be a possible mechanism of receptor activation. Finally, the addition of high concentrations of 1-thioglycerol promoted activation. Sulfhydryl groups may be involved in receptor subunit interaction.

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