STRESS, THE H-P-A AXIS, AND GROWTH AND DEVELOPMENT

Stress can be defined as an environmental transient challenging
homeostasis. Most organisms have developed "stress responses" that
buffer the stress or attenuate its effects. Examples include the
sporulation of bacteria and the estivation of amphibians. Perhaps the
best known and least understood stress response in mammals is activation
of the hypothalamic-pituitary-adrenal (HPA) axis. The mechanism by which
the hypothalamus stimulates the pituitary POMC cells to secrete ACTH and
other POMC products, the role of these products, and the role of the
consequent adrenal glucocorticoids in responding to stress is poorly
understood. This program project has three objectives. The first
objective is to better understand the array of hypothalamic hormones
regulating the pituitary POMC cell and the biochemical mechanisms by
which this regulation occurs. The second objective is to better
understand the stress related biologic effects of the specific molecular
elements of the HPA response to stress. The third objective is to more
precisely characterize the HPA response to stress in the human being and
to define its role in several "stress associated" disorders of growth and
development. To accomplish these objectives we have developed five
interacting projects using five shared facilities. The shared facilities
include tissue culture, radioimmunoassay, transgenic mouse,
histochemistry and administrative "cores".