AJP - Endocrinology and Metabolism, Vol 256, Issue 1 E74-E79, Copyright © 1989 by American Physiological Society
Effect of thyroid status on catecholamine stimulation of thyroxine 5'-deiodinase in brown adipocytes
I. Mills, A. Raasmaja, N. Moolten, G. Lemack, J. E. Silva and P. R. Larsen
Howard Hughes Medical Institute Laboratory, Boston, Massachusetts.
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.
