): The research plan is designed to study the modulation of the stress responses of the LHPA axis and its interaction with growth in the developing animal.
The specific aims are: (1) to understand the modulation of basal LHPA tone and LHPA inhibition by brain elements (particularly the hippocampus and hypothalamus) in developing rats; and (2) to examine the effect of repeated stress on both the LHPA and GH axis. Initial stages of the project will focus on determination of whether the hippocampus and relevant hippocampal projections modulate stress responsiveness and termination of stress in the developing rat in a manner similar to that of the adult. This will be followed by studies that focus on the disruption of the normal development of the stress responsiveness, termination, and GH axis parameters by chronic stress. The experimental procedures that will be employed include hippocampal and neural pathway lesions, in situ hybridization, receptor autoradiography, anatomic track tracing methods, morphological and morphometric methods, receptor binding, and radioimmunoassays (RIA).The broader significance of this research plan is to begin to understand the linkage between the GH and LHPA axes and their possible relations to the pathophysiology of stress- induced growth deficiency in humans, psychosocial dwarfism. The proposed program will provide the applicant with integrative training in the research areas of molecular genetics, histochemical methods, image analysis, anatomic circuitry, regulatory biochemistry, pharmacology, and endocrinology.