Type II glucocorticoid receptors in the CNS regulate metabolism in ob/ob mice independent of protein synthesis.
A single intracerebroventricular injection of dexamethasone rapidly (within 30 min) decreases brown adipose tissue thermogenesis by 25% as assessed by GDP binding and increases plasma insulin twofold in adrenalectomized ob/ob mice. The present study investigated the type of corticoid receptor(s) that mediate these effects and determined whether protein synthesis was necessary for expression of these glucocorticoid actions in ob/ob mice. Intracerebroventricular injection of aldosterone (a type I-corticoid receptor agonist) was ineffective in altering peripheral metabolism in adrenalectomized ob/ob mice, whereas RU-486 (a type II-corticoid receptor antagonist) abolished the effects of dexamethasone. Thus type II-like corticoid receptors, not type I receptors, mediated the rapid effects of dexamethasone in adrenalectomized ob/ob mice. Anisomycin (0.5 mg) administered subcutaneously almost completely suppressed (-92%) cerebral protein synthesis, but anisomycin did not abolish the rapid effects of dexamethasone in adrenalectomized ob/ob mice. Thus protein synthesis is not a prerequisite for rapid effects of dexamethasone in adrenalectomized ob/ob mice.
Chen
H L
HL
Department of Food Science and Human Nutrition, Michigan State University, East Lansing 48824-1224.
Romsos
D R
DR
D002001:Adipose Tissue, Brown / Q000378:metabolism; D000315:Adrenalectomy; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D015735:Mifepristone / Q000494:pharmacology; D009765:Obesity / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D014176:Protein Biosynthesis; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism*
D007328:Insulin; D011965:Receptors, Glucocorticoid; D006153:Guanosine Diphosphate; D015735:Mifepristone; D000841:Anisomycin; D003907:Dexamethasone