AJP - Endocrinology and Metabolism, Vol 252, Issue 3 E414-E419, Copyright © 1987 by American Physiological Society
Nuclear triiodothyronine receptor binding characteristics and occupancy in obese (ob/ob) mice
F. B. Hillgartner and D. R. Romsos
Obese (ob/ob) mice exhibit reduced adaptive thermogenesis associated with
an impairment of thyroid hormone action. The mechanism underlying the
latter defect was investigated by comparing the binding characteristics and
occupancy of solubilized nuclear 3,5,3'-triiodothyronine (T3) receptors
from livers of lean and obese mice. Scatchard analysis showed minimal
differences in Bmax and Kd between phenotypes at both 4 and 8-10 wk of age,
indicating that reduced hepatic thyroid hormone expression in obese mice is
not caused by alterations in nuclear receptor concentration or affinity. In
contrast, nuclear T3 receptor occupancy (endogenous T3 associated with the
specific receptor divided by Bmax) was 14 and 23% lower in 4- and 8- to
10-wk-old obese mice, respectively. Together with reported changes in
hepatic thyroid hormone-sensitive enzymes, these data are consistent with a
diminished nuclear T3 signal initiating thyroid hormone action in obese
mice. Decreased nuclear T3 receptor occupancy may be secondary to a low
transport of plasma T3 to the nuclear pool. In conclusion, impaired hepatic
thyroid hormone action in obese mice is mediated in part at least by a
reduction in nuclear T3 receptor occupancy.
