This Program Project focuses on the role of CRF superfamily peptides and their binding proteins, receptors and modulators in the integration of endocrine, autonomic, behavioral and immune responses to stress.
The first aim of this Program is to characterize physical interacfions between CRF family ligands, their receptors and binding proteins and to define motifs required to activate downstream signaling events.
The second aim i s to explore the physiologic and pathophysiologic significance of these molecules at the cellular and system levels and to study the control of protein expression and secretion as well as modes of action. Addressing questions of a complex ligand/receptor system is facilitated by the availability of key scientific tools. This core application is therefore designed to provide transgenic mice, antibodies, and immunoassays necessary to conduct the integrated studies proposed by the individual Projects. Transgenic mice over expressing components of the CRF system, or null-mutant mice lacking one or more CRFRs and/or ligands, are essential for elucidating the physiologic roles of these ligand and receptors in normal development and in disease states. Detection and/or neutralization of gene products in vitro and in vivo are dependent on high affinity and high titer antibodies of appropriate specificity against CRF family peptides and their soluble binding proteins and membrane bound receptors. Measurement of factors modulated by the CRF receptor-ligand system, including the pituitary hormone ACTH, the adrenal steroid corticosterone, and the pancreatic hormones insulin and glucagon, are also required. This Core can provide transgenic mice, high quality antibodies and assay services that require highly trained personnel and specialized equipment which would otherwise be unavailable to individual projects due to high cost. The establishment of a Core permits reduced costs, improved quality control, efficiency, specialization of technical personnel, standardization of protocols and the dedication of equipment and space. Core B is jointly directed by Drs. K.-F. Lee (transgenic mice unit, 5% effort) and W. Vale (antibody production and assay services, 3% effort).
;Integrated studies proposed by this Program aim to investigate of the CRF signaling network and will lead to the development of new means of treating stress-related and other serious human disorders, including treatment of insulin insensitivity disorders. The success of this Program is critically dependent on support services, including transgenic mice, high quality antibodies, and immunoassays, provided by Core B.
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