FIGURE 10.

Model of FOXO1 suppression of Lhb transcription in pituitary gonadotrope cells. A, Lhb repression is shown. In the absence of insulin signaling, FOXO1 is located in the nucleus of the cell where it blocks Lhb gene expression. Although FOXO1 does not bind to the proximal Lhb promoter containing EGR1, PTX1, and SF1 binding elements, the FOXO1 DBD is necessary for the suppression, suggesting that FOXO1 exerts its effect through protein-protein interactions with transcription factors/cofactors required for Lhb transcription. B, Lhb activation is shown. Activated IR/PI3K/AKT signaling leads to phosphorylation and nuclear export of FOXO1. Removal of FOXO1 repression results in increased Lhb synthesis.