Figure 2. Behavioral stress delays androgen ablation-induced prostate involution and apoptosis via β2-AR and BAD phosphorylation.

A) Stress attenuates bicalutamide-induced decrease in prostate weight of mice via ADRB2/BAD signaling. S = stressed; C = calm. Intact calm mice (0c), numbers under the columns indicate days of bicalutamide treatment; BAD^wt/wt mice with wild type BAD; BAD^wt/wt +ICI, mice treated with ICI118,551; BAD^3SA/WT, mice with knockin on phosphorylation-deficient BAD3SA mutant (n = 3 to 5 in each group). B) Microphotographs of dissected prostate glands from intact wild-type (0c), calm mice after 2 injections of bicalutamide (2c), and stressed mice after 2 injections of bicalutamide (2s). (C–H) Western blot and densitometric analysis of Western blots of proteins extracted from of anterior prostate glands of wild-type mice (BAD^WT/WT) (C, D); wild-type mice treated with ICI118,551 (ICI, BAD^WT/WT) (E, F); and transgenic mice that express phosphorylation-deficient mutant BAD (BAD^3SA/WT) (G, H). (C, E, G) Western blots conducted with antibodies to pSer133CREB (pCREB), pSer112BAD (pBAD), cleaved caspase 3 (c-casp3), cleaved PARP (cPARP) and β-actin. 3–4 representative samples for each treatment group are shown. Numbers over the Western blots show plasma epinephrine levels. Calm(BAD^WT/WT), mice with wild type BAD that were not stressed; 2BC(BAD^WT/WT), mice with wild type BAD that were given bicalutamide for 2 days and not stressed; 2BS(BAD^WT/WT), mice with wild type BAD that were given bicalutamide for 2 days and stressed; calm-ICI(BAD^WT/WT), mice with wild type BAD that were given ICI118,551 for 2days and not stressed; 2BC-ICI(BAD^WT/WT), mice with wild type BAD that were given bicalutamide and ICI118,551 for 2 days and not stressed; 2BS-ICI(BAD^WT/WT), mice with wild type BAD that were given bicalutamide and ICI118,551 for 2 days and stressed; calm(BAD^3SA/WT), mice with phosphorylation deficient mutated BAD that were not stressed; 2BC(BAD^3SA/WT), mice with phosphorylation deficient mutated BAD that were given bicalutamide for 2 days and not stressed; 2BS(BAD^3SA/WT), mice with phosphorylation deficient mutated BAD that were given bicalutamide for 2 days and stressed. (D, F, H) BAD and CREB phosphorylation was increased in stressed mice and reduced cleavage of caspase 3 and PARP was reduced in stressed mice treated with bicalutamide (*p<0.03). These effects were completely eliminated in mice injected with ICI118,551 (ICI) and in BAD3SA (BAD+/−) knock-in mice. Each experimental group contained at least 5 mice. Error bars represent SD from the average.