EFFECTS OF TRIIODOTHYRONINE ADMINISTRATION ON THE ADENYLYL-CYCLASE SYSTEM IN BROWN ADIPOSE-TISSUE OF RAT

This study was undertaken to investigate the effect of triiodothyronin e (T-3) administration to euthyroid rats on beta(3)-adrenoceptor (beta (3)-AR) expression and on the different components of the adenylyl cyc lase (AC) system in brown adipose tissue (BAT). In rats treated with T -3, the beta(3)-AR density (assessed by the binding of [H-3]CGP-12177) showed a decrease of 50%, as did their mRNA, as analyzed by reverse t ranscriptase-polymerase chain reaction. In hyperthyroid rats, compared with control rats, there was a 40% increase in G alpha(s) activity (s timulated by NaF or GTP gamma S) and a fourfold increase in the protei n concentration (Western blotting). In contrast, the level of the pert ussis toxin substrate G(i) declined by 35% in response to T-3. Analysi s of dose-response curves for isoproterenol and CGP-12177 revealed tha t neither basal nor stimulated AC activities nor 50% stimulatory conce ntration for these agonists was changed by T-3 administration. In conc lusion, these results suggest that downregulation of the beta(3)-AR by T-3 was counter-balanced by changes in other components of the AC cas cade (i.e., G(s) and G(i)), so no change occurred in the capacity of B AT to generate adenosine 3',5'-cyclic monophosphate.