FIGURE 11.

Proposed mechanism of cross-talk between estrogen and glucocorticoids. Upon ligand binding GR accumulates in the cell nucleus and is highly phosphorylated at Ser-211. The phosphorylated GR is transcriptionally active and binds as a homodimer to a specific palindromic DNA sequence, termed a GRE, located in the regulatory regions of target genes, such as MKP-1 and SGK. The induction of the target genes mediates the cell growth arrest. Estrogen induces the expression of PP5 that binds to the Ser-211-phosphorylated GR and dephosphorylates it, dampening its ability to bind GRE. Thus, the expression of glucocorticoid-inducible genes is inhibited. This supports estrogen-mediated cell proliferation.