Molecular signals for initiating protein synthesis in organ hypertrophy.

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Abstract
When chronically provoked to increased physiologic activity, organs increase in mass through augmented protein synthesis. This process of compensatory hypertrophy involved cell division and cell growth. To detect molecules that might regulate organ size by inducing hypertrophy, isolated, perfused, canine hearts were used in which the left ventricle was beating but performing no work. Hypertrophying hearts and kidneys and normal control organs were extracted and the extracts were perfused through isolated heart preparations. Before and after perfusion, RNA was extracted from fragments of the isolated hearts and translated in cell-free media containing [35S]methionine. Incorporation of methionine into protein was measured by liquid scintillation spectrometry. When perfused through normal hearts, extracts from hypertrophying heart and kidney were able to increase greatly the translational ability of RNA extracted from the normal hearts; corresponding perfusates from nonhypertrophying hearts and kidneys had no effect. Molecules that initiate hypertrophic organ growth are extractable, are generated by the cells of the organ under stress and are probably similar in heart, kidney and other organs.