The focus of the proposal is to understand the role of critical developmental periods which, when altered, lead to growth failure using the rat as an animal model. Efforts are concentrated on two stages of the rat's development, i.e., the first two weeks of life, when activation and termination of stress can be altered in opposite directions, depending on the timing of stressors and on the post-weaning period when the rat is no longer dependent upon maternal care for survival. Focus is placed upon the hypothalamus, hippocampus, and pituitary because these structures are thought to exert important neural and endocrine control upon the LHPA and the growth hormone (GH) axes. It is proposed to: 1) examine the consequences of early stress (maternal deprivation at specified times in life) on growth parameters; 2) examine if the individual differences in stress responsiveness resulting from maternal deprivation alter the expression of molecules linked to a functional GH axis during development; 3) attempt to revert the long-term negative effects of maternal deprivation by blocking the LHPA response to stress during early life with a CRH antagonist; and 4) explore psychopathology in families of children being seen for growth evaluation.
