Bottom, Fshb/FSHB promoter sequences from pig, human, sheep, and mouse were aligned to show the similarities and differences in the composite FBE2/SBE response element. There is a single base pair difference at the first position in pig (T) relative to the other species (C). As described in Ref. 43, this enables high-affinity binding of FOXL2 to the porcine, but not human, promoter. Top, Replacement of the C with a T (C→T) in human, ovine, and murine FSHB/Fshb promoter reporters confers enhanced activin sensitivity in LβT2 cells. The murine promoter differs at 2 bp from that of the pig in FBE2. Introduction of the porcine base pairs into the murine promoter (CA→TG) confers even greater activin sensitivity than the C→T base pair change alone. The data reflect the means (±SD or SEM) of 2 (human and sheep; n = 2) or 3 (mouse; n = 3) independent experiments, with treatments performed in duplicate or triplicate. Note the break in the y-axis.