Physicochemical analysis of glucocorticoid receptor in the immature pituitary gland: Evidence for lability and aggregation of the heat-activated form

The present study was aimed at characterizing the deficiency of the glucocorticoid-receptor system in the immature pituitary gland of neonatal rats. Under conditions of both constant protein and DNA concentrations, [³H]dexamethasone binding to nuclei was significantly lower in the immature, compared with the mature, glands, despite the comparable density of receptor sites. Chromatography on DEAE-Sephacel columns revealed the failure of the neonatal receptor to form stable activated complexes, although the dissociation of tracer from binding sites, as well as the magnitude of receptor activation, remained closely similar to those found for the adult binder. Also, a striking observation was that the immature receptor exhibited the property of forming more than twice as much inactive aggregate as the mature component, when heat-activated in presence of KCl. It thus seems that development of full expression of glucocorticoid-binding activity in the pituitary involves qualitative changes of both the receptor molecules and the cytoplasmic environment, that tend to enhance stability of the activated form of the binder.