Abstract

The purpose of this application is to determine the individual and cumulative effects of alcohol exposure, liver disease, and portal systemic shunting (a pre-requisite for portal systemic encephalopathy; PSE) on the neuroendocrine functioning of the hypothalamic-pituitary-gonadal axis. More specifically it is proposed to evaluate the pathogenetic role of gamma aminobutyric acid (GABA) in the syndrome of PSE and the neuroendocrine consequences of PSE with the use of an alpha and beta agonist of GABA and a GABA antagonist. Specifically the effects of alcohol, liver disease, PSE and the role of GABA in the pathogenesis of the observed alterations in LH, ACTH, and B endorphin secretion by the pituitary will be evaluated in rats in vivo and by rat pituitary and hypothalmic tissues studied in vitro. In addition, the effects of alcohol and liver disease with and without portal systemic shunting on accessory sex organ GABA- ergic ennervation and Sertoli cell secretion of transferrin and androgen binding protein will be evaluated. These studies should provide data essential to our understanding of the neuroendocrine and gonadal untoward effects of alcohol abuse, liver disease and hepatic encephalopathy. Using the data to be obtained as a result of these studies, it should be able to develop therapeutic protocols to be applied in an attempt to eliminate the common neuroendocrine abnormalities experienced by patients with alcoholism and liver disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AA004425-08
Application #
3479869
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1981-03-01
Project End
1992-02-28
Budget Start
1988-03-01
Budget End
1989-02-28
Support Year
8
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213

  Publications

Zhu, Q; Meisinger, J; Emanuele, N V et al. (2000) Ethanol exposure enhances apoptosis within the testes. Alcohol Clin Exp Res 24:1550-6
Deaciuc, I V; Alappat, J M; D'Souza, N B et al. (1998) Tumor necrosis factor-alpha internalization and degradation by isolated hepatocytes of rats exposed to ethanol. Alcohol 16:125-33
Gasbarrini, A; Borle, A B; Caraceni, P et al. (1996) Effect of ethanol on adenosine triphosphate, cytosolic free calcium, and cell injury in rat hepatocytes. Time course and effect of nutritional status. Dig Dis Sci 41:2204-12
Farghali, H; Caraceni, P; Rilo, H L et al. (1996) Biochemical and 31P-NMR spectroscopic evaluation of immobilized perfused rat Sertoli cells. J Lab Clin Med 128:408-16
Caraceni, P; Ryu, H S; van Thiel, D H et al. (1995) Source of oxygen free radicals produced by rat hepatocytes during postanoxic reoxygenation. Biochim Biophys Acta 1268:249-54
Caraceni, P; Van Thiel, D H; Borle, A B (1995) Dual effect of deferoxamine on free radical formation and reoxygenation injury in isolated hepatocytes. Am J Physiol 269:G132-7
Caraceni, P; Rosenblum, E R; Van Thiel, D H et al. (1994) Reoxygenation injury in isolated rat hepatocytes: relation to oxygen free radicals and lipid peroxidation. Am J Physiol 266:G799-806
Caraceni, P; Gasbarrini, A; Nussler, A et al. (1994) Human hepatocytes are more resistant than rat hepatocytes to anoxia-reoxygenation injury. Hepatology 20:1247-54
Caraceni, P; Yao, T; Degli Esposti, S et al. (1994) Effect of vitamin E on reoxygenation injury experienced by isolated rat hepatocytes. Life Sci 55:1427-32
Gasbarrini, A; Caraceni, P; Farghali, H et al. (1994) Effects of high and low pH on Ca2+i and on cell injury evoked by anoxia in perfused rat hepatocytes. Biochim Biophys Acta 1220:277-85

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