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"""""""".

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (SRC (LL))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Oregon Health and Science University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
New, M I; Nimkarn, S; Brandon, D D et al. (2001) Resistance to multiple steroids in two sisters. J Steroid Biochem Mol Biol 76:161-6
Slugg, R M; Hayward, M D; Ronnekleiv, O K et al. (2000) Effect of the mu-opioid agonist DAMGO on medial basal hypothalamic neurons in beta-endorphin knockout mice. Neuroendocrinology 72:208-17
Samuels, M H; Brandon, D D; Isabelle, L M et al. (2000) Cortisol production rates in subjects with suspected Cushing's syndrome: assessment by stable isotope dilution methodology and comparison to other diagnostic methods. J Clin Endocrinol Metab 85:22-8
Coste, S C; Kesterson, R A; Heldwein, K A et al. (2000) Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2. Nat Genet 24:403-9
Grahame, N J; Mosemiller, A K; Low, M J et al. (2000) Naltrexone and alcohol drinking in mice lacking beta-endorphin by site-directed mutagenesis. Pharmacol Biochem Behav 67:759-66
Grisel, J E; Mogil, J S; Grahame, N J et al. (1999) Ethanol oral self-administration is increased in mutant mice with decreased beta-endorphin expression. Brain Res 835:62-7
Brandon, D D; Isabelle, L M; Samuels, M H et al. (1999) Cortisol production rate measurement by stable isotope dilution using gas chromatography-negative ion chemical ionization mass spectrometry. Steroids 64:372-8
New, M I; Nimkarn, S; Brandon, D D et al. (1999) Resistance to several steroids in two sisters. J Clin Endocrinol Metab 84:4454-64
Grahame, N J; Low, M J; Cunningham, C L (1998) Intravenous self-administration of ethanol in beta-endorphin-deficient mice. Alcohol Clin Exp Res 22:1093-8
Abrami, L; Fivaz, M; Decroly, E et al. (1998) The pore-forming toxin proaerolysin is activated by furin. J Biol Chem 273:32656-61

Showing the most recent 10 out of 21 publications