Effect of thyroid status on catecholamine stimulation of thyroxine 5'-deiodinase in brown adipocytes.
We examined type II 5'-iodothyronine deiodinase activation by adrenergic agonists in dispersed brown adipocytes from euthyroid and hypothyroid rats. In euthyroid cells, basal deiodinase activity was 30-100 fmol I-.h-1.10(6) cells-1 and increased four- to fivefold during exposure to norepinephrine, an effect that was enhanced by alprenolol. In cells from hypothyroid rats, norepinephrine caused a three- to fourfold greater deiodinase stimulation than occurred in euthyroid cells but alprenolol inhibited the response. In euthyroid cells, phenylephrine caused greater stimulation than did norepinephrine, but this was inhibited by alprenolol. Isoproterenol and 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) inhibited the phenylephrine response but were modestly stimulatory alone. Although both alpha 1- and beta-adrenergic agonists increased deiodinase activity modestly in hypothyroid cells, in combination they caused a marked synergistic stimulation. This synergism was induced by 8-BrcAMP and forskolin, as well as by isoproterenol. The stimulation of deiodinase in both cell types was due to an increase in Vmax without an alteration in the Km and required mRNA synthesis. The markedly greater deiodinase response of the hypothyroid brown adipocyte to catecholamines may serve to enhance the impaired thermogenic response of this tissue to cold exposure.
Mills
I
I
Howard Hughes Medical Institute Laboratory, Boston, Massachusetts.
Raasmaja
A
A
Moolten
N
N
Lemack
G
G
Silva
J E
JE
Larsen
P R
PR
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D002001:Adipose Tissue, Brown / Q000201:enzymology*; D000526:Alprenolol / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D007037:Hypothyroidism / Q000201:enzymology*; D007453:Iodide Peroxidase / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002395:Catecholamines; D003609:Dactinomycin; D005576:Colforsin; D010656:Phenylephrine; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000526:Alprenolol; D003513:Cycloheximide; D007453:Iodide Peroxidase; D007545:Isoproterenol; D009638:Norepinephrine; D011224:Prazosin