General effect of endotoxin on glucocorticoid receptors in mammalian tissues
Considering the ubiquitous nature of glucocorticoid actions and the fact that endotoxin inhibits glucocorticoid action in the liver, we proposed to examine whether endotoxin affected extrahepatic actions of glucocorticoids. Fasted C57BL/6J mice were injected intraperitoneally with endotoxin (LD50) at 0800 and were killed 6 h later. Control mice were injected with an equal volume of saline. /sup 3/H-dexamethasone binding, measured by a new cytosol exchange assay utilizing molybdate plus dithiothreitol, in liver, kidney, skeletal muscle, spleen, lung, and heart tissue was significantly lower in treated than in control mice. The equilibrium dissociation constants were not significantly different, but the number of available binding sites in each tissue was reduced by endotoxin treatment. Phosphoenolpyruvate carboxykinase activity was significantly reduced in liver but not in kidney. Endotoxin treatment lowered glycogen content in liver but not in skeletal muscle. The reduction observed in the a form of liver glycogen synthase due to endotoxin was not seen in skeletal muscle glycogen synthase a. These data support the proposal that endotoxin or a mediator of its action inhibits systemic glucocorticoid action. The results also emphasize the central role of the liver in the metabolic disturbances of the endotoxin-treated mouse.
- Research Organization:
- Univ. of Oklahoma Health Sciences Center, Oklahoma City
- OSTI ID:
- 5623471
- Journal Information:
- Circ. Shock; (United States), Vol. 4
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ENDOTOXINS
BIOLOGICAL EFFECTS
GLUCOCORTICOIDS
INHIBITION
RECEPTORS
DEXAMETHASONE
GLYCOGEN
HEART
INTRAPERITONEAL INJECTION
KIDNEYS
LIVER
LUNGS
MICE
MUSCLES
PHOSPHOTRANSFERASES
SALMONELLA TYPHIMURIUM
SPLEEN
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ADRENAL HORMONES
ANIMALS
ANTIGENS
BACTERIA
BODY
CARBOHYDRATES
CARDIOVASCULAR SYSTEM
CORTICOSTEROIDS
DIGESTIVE SYSTEM
ENZYMES
GLANDS
HORMONES
HYDROXY COMPOUNDS
INJECTION
INTAKE
ISOTOPE APPLICATIONS
KETONES
LABELLED COMPOUNDS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MICROORGANISMS
ORGANIC COMPOUNDS
ORGANS
PHOSPHORUS-GROUP TRANSFERASES
POLYSACCHARIDES
PREGNANES
PROTEINS
RESPIRATORY SYSTEM
RODENTS
SACCHARIDES
SALMONELLA
STEROID HORMONES
STEROIDS
TOXIC MATERIALS
TOXINS
TRANSFERASES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques