['Postnatal growth of the heart chiefly involves nonproliferative cardiomyocyte enlargement. Cardiac hypertrophy exists in a "physiological" form that is an adaptive response to long-term exercise training and as a "pathological" form that often is a maladaptive response to provocative stimuli such as hypertension and aortic valvular stenosis. A signaling cascade that includes the protein kinase Akt regulates the growth and survival of many cell types, but the precise role of Akt1 in either form of cardiac hypertrophy is unknown.', 'To evaluate the role of Akt1 in physiological cardiac growth, akt1(-/-) adult murine cardiac myocytes (AMCMs) were treated with IGF-1, and akt1(-/-) mice were subjected to exercise training. akt1(-/-) AMCMs were resistant to insulin-like growth factor-1-stimulated protein synthesis. The akt1(-/-) mice were found to be resistant to swimming training-induced cardiac hypertrophy. To evaluate the role of Akt in pathological cardiac growth, akt1(-/-) AMCMs were treated with endothelin-1, and akt1(-/-) mice were subjected to pressure overload by transverse aortic constriction. Surprisingly, akt1(-/-) AMCMs were sensitized to endothelin-1-induced protein synthesis, and akt1(-/-) mice developed an exacerbated form of cardiac hypertrophy in response to transverse aortic constriction.'] Is akt1 required for physiological cardiac growth?