One of the major features of growth is the accretion of protein. During perinatal growth proteins may accumulate by enhanced rates of protein synthesis and/or reduced rates of protein degradation. Control of protein turnover during fetal and early postnatal growth may be regulated by hormonal and nutritional factors, some of which may be unique to the perinatal period. The long-term objectives of this proposal are to gain a more detailed understanding of factors regulating protein turnover in the perinatal period during altered physiological states which perturb fetal and early postnatal growth and to test the hypothesis that lysosomal proteolysis is relatively unimportant in fetal skeletal muscle. Both in vivo and in vitro techniques will be used to study protein turnover in the fat fetus following maternal caloric and protein deprivation, as well as in states of fetal insulin deficiency and excess. The influence of postnatal hypothyroidism and malnutrition on protein turnover will also be assessed. Previous studies suggest that lysomomal proteolysis is deficient in fetal muscle. Studies to provide further evidence for this hypothesis will include analysis of protein breakdown in vitro in muscle from fetal and newborn rats under conditions known to affect lysosomal proteolysis in the juvenile rat, such as fasting and nurtitional/hormonal omission from incubation medium. Subcellular distribution and immunocytochemical location of lysosomal enzymes in muscles from fetal vs. young adults will be determined. An attempt will be made to dissect the pathway of lysosomal enzyme biosynthesis and processing by using skeletal muscle in tissue culture from fetal vs. junvenile rats. These studies should improve our understanding of factors regulating protein turnover in the fetus and, as a corollary, of mechanisms controlling fetal growth. Fetal growth retardation in humans is a major problem and understanding what factors contribute to growth retardation and how they do so may eventually help reduce the frequency of intrauterine growth retardation in the human.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD015243-06
Application #
3313006
Study Section
Metabolism Study Section (MET)
Project Start
1982-04-01
Project End
1989-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
6
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of New Mexico
Department
Type
Schools of Medicine
DUNS #
829868723
City
Albuquerque
State
NM
Country
United States
Zip Code
87131
Johnson, J D; Greenberg, R E (1992) Protein turnover in rat placenta: effects of maternal fasting and maternal protein restriction. Placenta 13:141-50
Johnson, J D; Wogenrich, W J; Hsi, K C et al. (1991) Growth retardation during the suckling period in expanded litters of rats: observations of growth patterns and protein turnover. Growth Dev Aging 55:263-73
Johnson, J D; Dunham, T; Wogenrich, F J et al. (1990) Fetal hyperinsulinemia and protein turnover in fetal rat tissues. Diabetes 39:541-8
Johnson, J D; Dunham, T (1988) Protein turnover in tissues of the fetal rat after prolonged maternal malnutrition. Pediatr Res 23:534-8
Johnson, J D; Dunham, T; Skipper, B J et al. (1986) Protein turnover in tissues of the rat fetus following maternal starvation. Pediatr Res 20:1252-7
Johnson, J D (1985) Protein turnover in brain of the rat fetus. J Neurochem 44:260-4
Johnson, J D (1985) Regulation of fetal growth. Presidential address, Society for Pediatric Research, May 1984. Pediatr Res 19:738-41