Abstract

The objectives of this work are to understand the neural control of ACTH secretion and the function of the adrenocortical system (ACS) in the overall physiology of the animal. Glucocorticoids secreted by the adrenals are necessary for normal mammalian life. In their absence, even minor stress may provoke collapse and death. Understanding of the regulation of function and the physiological effects of normal ACS activity is, therefore, of basic and clinical significance. The studies proposed are based on previous and current results from the lab, and are designed to further knowledge about brain control components of the system and the life saving effects of corticosterone (B). The grant has 4 specific aims: 1. Using streptozotocin-induced diabetes as a chronic stress in rats, the effects of this on hippocampus, hypothalamus, pituitary and adrenal components of the system will be determined, measuring B receptors, hypothalamic secretogogues, ACTH and B. The sensitivity of these components will be compared to that in non-stressed rats. 2. Brain negative feedback sites for B will be determined in rats using a combined lesion and B-implantation approach with measurement of ACTH. 3. The function of neurotransmitters known to arise from nearby nuclei involved in energy metabolism and to innervate corticotropin- releasing factor cells in the paraventricular nuclei will be determined by microinjection and measurement of ACTH; small lesions in these nuclei will be made and the effects of these on feeding- or fasting-induced changes in ACS activity will be tested. 4. The role of glucose in enabling a homeostatic response of adrenalectomized rats to stress will be tested using infusions of glucose and blockage of gluconeogenesis. Regulation of function in the rat ACS closely resembles that in man. The results of these studies should provide new insights into the mechanisms which underlie ACS malfunction in people with chronic diseases, adrenal enzyme deficiencies, eating disorders and depression.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
4R37DK028172-14
Application #
2138104
Study Section
Special Emphasis Panel (NSS)
Project Start
1981-07-01
Project End
1997-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
14
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Physiology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Ginsberg, Abigail B; Pecoraro, Norman C; Warne, James P et al. (2010) Rapid alteration of stress-induced hypothalamic-pituitary-adrenal hormone secretion in the rat: a comparison of glucocorticoids and cannabinoids. Stress 13:248-57
Warne, James P; Akana, Susan F; Ginsberg, Abigail B et al. (2009) Disengaging insulin from corticosterone: roles of each on energy intake and disposition. Am J Physiol Regul Integr Comp Physiol 296:R1366-75
Warne, James P; Padilla, Benjamin E; Horneman, Hart F et al. (2009) Metabolic and neuroendocrine consequences of a duodenal-jejunal bypass in rats on a choice diet. Ann Surg 249:269-76
Foster, Michelle T; Warne, James P; Ginsberg, Abigail B et al. (2009) Palatable foods, stress, and energy stores sculpt corticotropin-releasing factor, adrenocorticotropin, and corticosterone concentrations after restraint. Endocrinology 150:2325-33
Akana, Susan F (2008) Feeding and stress interact through the serotonin 2C receptor in developing mice. Physiol Behav 94:569-79
Warne, James P; Foster, Michelle T; Horneman, Hart F et al. (2008) The gastroduodenal branch of the common hepatic vagus regulates voluntary lard intake, fat deposition, and plasma metabolites in streptozotocin-diabetic rats. Am J Physiol Endocrinol Metab 294:E190-200
Warne, J P; Horneman, H F; Akana, S F et al. (2008) Insulin and the constituent branches of the hepatic vagus interact to modulate hypothalamic and limbic neuropeptide mRNA expression differentially. J Neuroendocrinol 20:1067-77
Warne, J P; Horneman, H F; Ginsberg, A B et al. (2007) Mapping brain c-Fos immunoreactivity after insulin-induced voluntary lard intake: insulin- and lard-associated patterns. J Neuroendocrinol 19:794-808
Warne, James P; Foster, Michelle T; Horneman, Hart F et al. (2007) Afferent signalling through the common hepatic branch of the vagus inhibits voluntary lard intake and modifies plasma metabolite levels in rats. J Physiol 583:455-67
Dallman, Mary F; Warne, James P; Foster, Michelle T et al. (2007) Glucocorticoids and insulin both modulate caloric intake through actions on the brain. J Physiol 583:431-6

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