Characterization of transiently and constitutively expressed progesterone receptors: Evidence for two functional states

Activated steroid receptors induce chromatin remodeling events in the promo ters of some target genes. We previously reported that transiently expresse d progesterone receptor (PR) cannot activate mouse mammary tumor virus (MMT V) promoter when it adopts the form of ordered chromatin. However, when exp ressed continuously, the PR acquires this ability. In this study we explore d whether this gain of function occurs through alterations in nucleoprotein structure at the MMTV promoter or through changes in receptor status. We o bserved no major structural differences at the MMTV promoter in the presenc e of constitutively expressed PR and found its mechanism of activation to b e very similar to that of the glucocorticoid receptor (GR). However, a syst ematic comparison of the functional behavior of the transiently and constit utively expressed PR elucidated significant differences. The transiently ex pressed PR is activated in the absence of ligand by cAMP and by components in FBS and has significantly increased sensitivity to progestins. In contra st, the constitutively expressed PR is refractory to activation by cAMP and serum and has normal sensitivity to its ligand. In addition, while the PR is localized to the nucleus in both cases, a significant fraction of the tr ansiently expressed PR is tightly bound to the nucleus even in the absence of ligand, while the majority of constitutively expressed PR is not. These results strongly suggest that the PR undergoes processing in the cell subse quent to its initial expression and that this processing is important for v arious aspects of its function, including its ability to productively inter act with target genes that require chromatin remodeling for activation.