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).

Public Health Relevance

;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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-7 (J1))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Salk Institute for Biological Studies
La Jolla
United States
Zip Code
Spierling, Samantha R; Mattock, Maegan; Zorrilla, Eric P (2017) Modeling hypohedonia following repeated social defeat: Individual vulnerability and dopaminergic involvement. Physiol Behav 177:99-106
Erchegyi, Judit; Wang, Lixin; Gulyas, Jozsef et al. (2016) Characterization of Multisubstituted Corticotropin Releasing Factor (CRF) Peptide Antagonists (Astressins). J Med Chem 59:854-66
Pilbrow, Anna P; Lewis, Kathy A; Perrin, Marilyn H et al. (2016) Cardiac CRFR1 Expression Is Elevated in Human Heart Failure and Modulated by Genetic Variation and Alternative Splicing. Endocrinology 157:4865-4874
Zhang, Cheng; Kuo, Ching-Chang; Moghadam, Setareh H et al. (2016) Corticotropin-releasing factor receptor-1 antagonism mitigates beta amyloid pathology and cognitive and synaptic deficits in a mouse model of Alzheimer's disease. Alzheimers Dement 12:527-37
Cui, Changhai; Noronha, Antonio; Warren, Kenneth R et al. (2015) Brain pathways to recovery from alcohol dependence. Alcohol 49:435-52
Perrin, Marilyn H; Tan, Laura A; Vaughan, Joan M et al. (2015) Characterization of a Pachymedusa dacnicolor-Sauvagine analog as a new high-affinity radioligand for corticotropin-releasing factor receptor studies. J Pharmacol Exp Ther 353:307-17
Zhang, Cheng; Kuo, Ching-Chang; Moghadam, Setareh H et al. (2015) Corticotropin-Releasing Factor Receptor-1 Antagonism Reduces Oxidative Damage in an Alzheimer’s Disease Transgenic Mouse Model. J Alzheimers Dis 45:639-50
van der Meulen, Talitha; Huising, Mark O (2015) Role of transcription factors in the transdifferentiation of pancreatic islet cells. J Mol Endocrinol 54:R103-17
Radley, Jason J; Sawchenko, Paul E (2015) Evidence for involvement of a limbic paraventricular hypothalamic inhibitory network in hypothalamic-pituitary-adrenal axis adaptations to repeated stress. J Comp Neurol 523:2769-87
van der Meulen, Talitha; Donaldson, Cynthia J; Cáceres, Elena et al. (2015) Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion. Nat Med 21:769-76

Showing the most recent 10 out of 382 publications