Fig. 5: Evaluation of SR parameters by direct measurement of SR in cultured cells.

a Normalized bioluminescence of PER2::LUC at SR measurement using dexamethasone (DEX), forskolin (FK), and corticosterone (CORT). The concentration of each line corresponds to that in (b) and (c). b Dose-response curve of SR amplitude. Each parameter was obtained by fitting it to the Hill equation. c Change in SR phase with different concentrations. The blank circle is individual data, and the filled square is the mean value. d, e Changes in SR amplitude for mixed stimuli of the combination of DEX and FK (d), and DEX and CORT (e). f, g SR amplitudes (f) and phase (g) for the combination of DEX and FK are estimated by the sum of SR parameters for each stimulus. h, i SR amplitudes for the combination of DEX and CORT are estimated by the sum of SR parameters (h) and equivalent concentration (i). Filled circles indicate the results of single stimuli, and blank circles show the results of mixed stimuli. j, k Change in SR amplitude for DEX with DEX background in experiment (j) and model (k). l, m Change in SR amplitude for 100 nM DEX (l) and 100 μM FK (m) with different background: no background, 100 nM DEX, 100 nM CORT, or 100 μM FK (*p < 0.05, **p < 0.01, ***p < 0.001; two-tailed t-test). Exact p-values are provided in Source Data. n, o Change in SR amplitude (n) and phase (o) for the combination of 100 nM DEX and mifepristone (MF). The blank circle is individual data, and the filled square is the mean value. p, q Relationship between SR phase and SR amplitude for DEX and CORT stimulation (p) and MF stimulation (q). “BK” indicates the background stimuli, and “ADD” indicates the additional stimuli. Each individual data indicates the results of independent experiments and experiments were performed three times or more. SR singularity response.