The long range aim of this project is to elucidate controls of catch-up (compensatory) growth, the acceleration of growth which occurs after a period of growth retardation in the child or young animal, and proportionate growth, the maintenance of normal relative sizes of body parts. The experiments will be performed on rats which will consist of controls or animals undergoing treatment or post treatment recovery after neonatal X-irradiation of the head; high dose cortisone treatment; fasting; or propylthiouracil-induced hypothyroidism. These treatments all produce growth retardation, but they differ in the degree of catch-up growth during recovery. The proposed experiments will test the possibility that these controls are located in the brain, that the catch-up growth control consists of a sensor for existing body size, a reference (setpoint) normal size, and a regulator of the growth rate. The work will examine the possible relationship of growth hormone secretion to catch-up growth, the interaction of the environmental light/dark cycle with pulsatile growth hormone release, and the relationship this may have to the innate 24-hour biologic clock in the rat as evidenced by running activity cycles in optic nerve sectioned rats. Experiments will be carried out to determine the inter-relationship of increased growth hormone secretion in catch-up growth to somatostatin levels in plasma in the superior vena cava and the hepatic portal vein, and to feeding and drinking behavior. Rat IGF-I and IGF-II (MSA) and thymidine inhibitor activity will be determined in serum during growth arrest and recovery in the experimental models in order to assess the possible roles these factors have in catch-up growth recovery. Partial brain irradiation and selective lesions will be produced in brain in order to localize controls of catch-up and proportionate growth. Information produced by this research will increase our understanding of the mechanisms involved in normal growth as well as in a variety of pathological states. This will have an application to the understanding of growth control in normal and abnormal states in the human. This improved understanding may lead to therapeutic approaches for abnormal growth in children.
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