Incubation of hamster uterine cytosol with millimolar concentrations of sodium molybdate prior to addition of labeled steroid increased recovery of progesterone receptor 2-fold. This stabilizing effect of molybdate was also manifest on gel electrophoresis of the receptor. In the absence of molybdate, no specific [3H] progesterone binding was detectable on polyacrylamide gel electrophoresis. But, in the presence of 5 mM sodium molybdate, a [3H]progesteronebinding species was clearly evident on the gels. The radioactivity associated with this binder was displaceable by unlabeled progesterone but not by cortisol and depended on the concentration of [3H]progesterone employed, suggesting that this binding species is a progesterone receptor. Molybdate treatment produced a small increase in receptor size on low-salt sucrose gradients (from 6-7 S to 7.5 S). There was no effect of molybdate on receptor sedimentation in the presence of high salt (0.3 M KC1). Further analysis of this phenomenon by gel filtration suggested that this molybdate-mediated increase in receptor size was due to receptor aggregation. In low-salt buffers, molybdate treatment markedly increased the proportion of receptors contained in large aggregates (Stokes radius >8.0 nm). Again, this effect was abolished in the presence of high salt. In conjunction with receptor stabilization, molybdate prevented binding of uterine progesterone receptor to DNA-cellulose. These findings suggest that sodium molybdate stabilizes the unliganded, unactivated form of the receptor. Moreover, these effects seem to be mediated through a direct interaction of molybdate with the receptor, one which results in receptor aggregation.
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