A summary of the postulated role of RB in Sertoli cells. In wild-type (WT) Sertoli cells, inhibition of E2F3a by RB prevents expression of E2F1. In Rb cKO Sertoli cells, the aberrant activation of E2F3a and, thus, E2F1 leads to derepression of cell cycle and apoptotic genes. RB may also modulate the expression of AR-regulated genes in WT Sertoli cells; therefore, the lack of RB in Rb cKO Sertoli cells may directly lead to their misregulation. Repression of E2F3a by RB may be responsible for AR-independent gene changes involved in adult Sertoli cell function (i.e. Timp1 down-regulation).