Rescue of hLHR and hFSHR misfolded mutants by pharmacoperones. (A) Measurement of cAMP accumulation by CRE-luciferase reporter gene activaton after 24 h stimulation in cells expressing Wt (●), A593P mutant (■), or S616Y (▲) mutant hLHRs was determined over a range of concentrations of Org 42599. Data were fitted by sigmoidal dose-response curves with Hill coefficients of unity and are presented as fold versus basal values for each receptor (mean ± SEM from at least three independent experiments). (B) Org41841 rescues Wt hFSHR and mutant A189V (p= 0.002), but is unable to rescue other mutants with mutation at diverse sites in the molecule (SEMs shown). After transfection and incubation in Org41841, cellular response was assessed by a challenge with 100 ng hFSH. As mutants were obtained from different laboratories and were in different expression vectors, controls are shown with the corresponding Wt hFSHR and the empty vector in each case. Figure 3A is reproduced from Newton et al. (2011), with permission of the National Academy of Sciences USA; figure 3B is reproduced from Janovick et al. (2009) with permission of Elsevier Ireland Ltd.