Glucocorticoids modulate beta-adrenoceptor subtypes and adenylate cyclase in brown fat.
Thermogenesis in brown adipose tissue (BAT) serves as a regulator of body temperature and weight maintenance. Thermogenesis can be stimulated by catecholamine activation of adenylate cyclase through the beta-adrenergic receptor. Glucocorticoids potentiate the action of catecholamines in some tissues by increasing the expression of beta-adrenergic receptors. Paradoxically, glucocorticoids suppress and adrenalectomy enhances BAT thermogenesis. To further study the reasons for this discrepancy, we assessed the effects of methylprednisolone administration, adrenalectomy, and adrenalectomy with corticosterone replacement on adenylate cyclase activity in BAT and on beta-adrenergic receptor density in lungs and BAT of rats. In lungs, the density of the beta 2-adrenergic receptor subtype increases after methylprednisolone administration and decreases after adrenalectomy. There was no change in BAT receptor density, but isoproterenol-, NaF-, and forskolin-stimulated adenylate cyclase activity was reduced by 20-35% after methylprednisolone treatment. There was a two- to threefold increase in adenylate cyclase activity after adrenalectomy, which was reversed by corticosterone administration. These data suggest that one mechanism by which glucocorticoids regulate BAT thermogenesis is by modulating the beta-adrenergic pathway at the level of adenylate cyclase activation.
Scarpace
P J
PJ
Geriatric Research, Education, and Clinical Center, Veterans Administration Medical Center, Gainesville 32602.
Baresi
L A
LA
Morley
J E
JE
D000262:Adenylyl Cyclases / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000315:Adrenalectomy; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects; D003345:Corticosterone / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values
D011943:Receptors, Adrenergic, beta; D003576:Electron Transport Complex IV; D000262:Adenylyl Cyclases; D003345:Corticosterone; D008775:Methylprednisolone