Simulation of normal protein accretion in rats.

A dynamic model of growth in rats has been developed based on the application to whole-body protein of terms previously identified in relationship to hyperplasia and hypertrophy of individual mammalian tissues and organs. Differential equations determined to be the simplest adequate to simulate postweaning growth patterns describe DNA accretion, protein synthesis and protein degradation. Maximum cell number (DNAMX) and cell size (protein/DNA) are implicit in the equations as genetically specified regulators of growth. Effects of differences in mature size on patterns of growth are accommodated by adjusting rate constants such that at equal maturity, rates are proportional to mature size to the 0.73 power. The sensitivity of the model was tested for independently derived parameter values and all deduced parameters. Model behavior is sensitive to the definition of DNAMX but is relatively insensitive to other parameter values. In particular, protein synthesis and degradation rates are highly correlated so that an independent estimate of one or the other is required to define the model. Rate constants optimized with respect to data on DNA and protein accretion in male Sherman rats (DNAMX = 429 mg) were used to simulate growth of male Sprague-Dawley rats (DNAMX = 150 mg). Good agreement was obtained between observed and predicted values with no systematic error of prediction.