Because poor intrauterine growth accounts for as much as 40% of the population of low birth weight infants, understanding the factors that alter fetal growth, their relative importance, and the means by which they exert their effects is vital. Fetal growth is the accretion of the various components of fetal body composition, including protein. Protein accretion is the imbalance between the synthesis and breakdown of protein. These,. processes are modified by the same two groups of factors reported to modify fetal growth, substrate availability and hormonal regulation. One of the principal substrates needed for protein synthesis is energy. The long term aim of this proposal is, therefore, to begin to test the hypothesis that energy availability is an important modulator of the synthesis, breakdown, and accretion of protein in the late gestation sheep fetus . Specifically, we propose that conditions (decreased oxygen availability, catecholamine infusion) that decrease fetal oxidative potential will decrease protein accretion by decreasing protein synthesis more than breakdown. Conditions that increase fetal oxidative state (decreased glucose availability, hypoinsulinemia, cortisol infusion) will not decrease protein synthesis. Under these latter conditions, any decrease in protein accretion that occurs must occur because protein breakdown increases. To test this concept, under control and each of six experimental conditions in ovine fetuses the following variables will be measured and compared: (1) lactate/pyruvate ratio as an index of cytosolic redox state, (2) the rate of leucine use for protein synthesis,, breakdown, and accretion, (3) the delivery to the fetus of oxygen, glucose, lactate, and[ amino acids, and (4) the fetal concentrations of insulin, glucagon, and catecholamines. The six experimental conditions to be studied are: (1) Decreased oxygen availability (low maternal inspired oxygen concentration), (2) Decreased glucose availability (maternal hyperinsulinemic hypoglycemia), (3) Hypoinsulinemia (fetal pancreatic clamp without insulin replacement), (4) Cortisol infusion during fetal pancreatic clamp, (5) Norepinephrine infusion during fetal pancreatic clamp, and (6) Epinephrine infusion during fetal pancreatic clamp. These studies should enhance our understanding of the control of fetal growth and allow more informed clinical decisions. For example, understanding that there are different reasons for decreased fetal protein accretion (and so fetal growth) will preclude the mistaken assumption that all fetal growth deficits will be amenable to a single remedy.
