CBG limits hepatic corticosterone uptake. Liver minces were incubated with [3H]-corticosterone in PBS or the indicated plasma source for 30 minutes. A, [3H]-corticosterone (Mean ± SEM CPM) in the liver were lower in samples containing CBG in the incubation media, indicated by a main effect of experimental condition (F [2, 30] = 40.06, P < .0001). B, In the incubation media, [3H]-corticosterone levels were higher in samples containing CBG (F [2, 30] = 100.8, P < .0001). There was also a main effect of sex (F [1, 30] = 43.24, P < .0001) whereby females retained more [3H]-corticosterone in the incubation media compared to males. C, The ratio of [3H]-corticosterone to total [3H] was used to assess the extent of [3H]-corticosterone metabolism. In the liver, there was a main effect of sex (F [1, 28] = 126.1, P < .0001) whereby males showed greater metabolism than females. In the incubation media, there was lower metabolism in samples containing CBG (F [2, 30] = 44.8, P < .0001). There was also a main effect of sex (F [1, 30] = 26.39, P < .0001), wherein females showed lower [3H]-corticosterone metabolism than males. N = 6 per group. M = male, F = female, WT = wild-type, KO = CBG-knockout. CPM = counts per minute.