Epinephrine (E) and norepinephrine (NE) basal excretion, and beta2-adrenergic (β2) receptor content are altered after overtraining (OT). Recent literature implicates β2 signaling in the maintenance of skeletal muscle mass and phenotype. β2 signaling in skeletal muscle involves the signaling protein extracellular signal-regulated kinase (ERK). To date, no study has investigated the E-β2-ERK signaling axis in OT humans. PURPOSE: To determine if basal sensitivity of epinephrine (E/β2) and norepinephrine (NE/β2) were related to changes in ERK activity following a period of resistance exercise OT. METHODS: Sixteen males were randomized into an overtraining group (OT: n=8, age=20.6 ± 2.1yrs, ht=179±10cm, body mass= 78.6±12.1kg) or control group (CON n=8, age=19.8±1.7yrs, ht=179±6cm, body mass=76.7±9.7kg). The OT group performed 10 X 1 at 100% 1 RM daily for 2 wks. CON performed normal training 2 days/wk. Muscle biopsies from the vastus lateralis muscle and nocturnal urinary E and NE were assessed before (pre) and after (post) overtraining. Biopsies were analyzed for total-ERK and ratio of phosphorylated ERK (pERK) via western blotting. The ratio of pERK was corrected for changes in total-ERK content between pre and post training. Multiple regression was used to determine if E/β2 and NE/β2 (independent variables) were significantly related to changes in pERK (dependent variable) after training. Significance was set at p<.05. RESULTS: When groups were analyzed together, E/β2 and NE/β2 at pre explained 64% of variance in the change of pERK at post (F[2,13]=14.4, p=.001, adj. R2=.641). When analyzed separately, OT E/β2 and NE/β2 at pre explained 78% of variance in the change of pERK at post (F[2,5]=13.2, p=.01, adj. R2=.778). Both independent variables significantly contributed to the model (E/β2: b=-1.05, t=-4.89, p<0.001; NE/β2: b=1.07, t=4.99, p<0.001). In CON, E/β2 and NE/β2 at pre did not explain any variance in pERK at post (F[2,5]=.035, p=.966, adj. R2=.014). CONCLUSION: While preliminary, it appears subjects with lower catecholamine sensitivity prior to stressful training may be predisposed for greater down-regulation of ERK after OT. Furthermore, while β2 sensitivity is related to impaired ERK activity after OT, ERK activity following normal training is likely mediated in part, by other mechanisms.