Nuclear triiodothyronine receptor binding characteristics and occupancy in obese (ob/ob) mice
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 (T/sub 3/) receptors from livers of lean and obese mice. T/sub 3/ concentration was measured by radioimmunoassay. Scatchard analysis showed minimal differences in B/sub max/ and K/sub d/ 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 T/sub 3/ receptor occupancy (endogenous T/sub 3/ associated with the specific receptor divided by B/sub max/) 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 T/sub 3/ signal initiating thyroid hormone action in obese mice. Decreased nuclear T/sub 3/ receptor occupancy may be secondary to a low transport of plasma T/sub 3/ 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 T/sub 3/ receptor occupancy.
- Research Organization:
- Michigan State Univ., East Lansing
- OSTI ID:
- 5301064
- Journal Information:
- Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States) Vol. 252:3; ISSN AJPHA
- Country of Publication:
- United States
- Language:
- English
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62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
CHROMATIN
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
HORMONES
IMMUNOASSAY
IMMUNOLOGY
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIVER
MAMMALS
MEMBRANE PROTEINS
METABOLIC DISEASES
MICE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PROTEINS
RADIOASSAY
RADIOIMMUNOASSAY
RADIOIMMUNOLOGY
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RODENTS
THYROID HORMONES
TRACER TECHNIQUES
TRIIODOTHYRONINE
VERTEBRATES