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Starvation-induced decrease in the maximal binding capacity for triiodothyronine of the thyroid hormone receptor is
T Tagami1, H Nakamura, S Sasaki
1Department of Internal Medicine, Kyoto University School of Medicine, Japan.
Abstract:
Biological responses to thyroid hormones are mediated by the nuclear thyroid hormone receptor (TR). Alterations in the maximal triiodothyronine (T3)-binding capacity (Cmax) of TR measured using a ligand binding assay have been reported under some pathophysiological conditions. Northern blot analysis has indicated that TR mRNA concentrations do not necessarily correlate with Cmax levels. For example, although the decrease in Cmax in rat liver induced by prolonged fasting is well established, TR mRNA concentrations have been reported to be constant. In the present study, we examined starvation-induced changes in TR by Western blot with anti-TR(alpha 1 + beta)antiserum and by Scatchard plot analysis. Starvation of rats for 72 hours decreased Cmax in the liver to 72.5% of control levels. The 47- and 55-kd TR proteins detected in hepatic nuclear extract by Western blotting also decreased to 64% and 66% of control values, respectively. The starvation-induced changes in Cmax and TR protein levels paralleled the change in total hepatic nuclear protein concentration. These results suggest that the decrease in T3-binding activity of the TR is due to a reduction of the TR protein itself.
Insights
Starvation reduces thyroid hormone receptor (TR) binding capacity in rat liver. This decrease is linked to lower TR protein levels, not mRNA, suggesting protein reduction drives altered T3 binding during fasting.
Area of Science:
- Endocrinology
- Molecular Biology
- Cellular Biology
Background:
- Thyroid hormone receptor (TR) mediates biological responses to thyroid hormones.
- Alterations in TR's maximal triiodothyronine (T3)-binding capacity (Cmax) occur in pathophysiological states.
- TR mRNA levels do not consistently correlate with Cmax, as seen in fasting models.
Purpose of the Study:
- To investigate starvation-induced changes in thyroid hormone receptor (TR) protein levels and T3-binding capacity.
- To determine if changes in TR protein or mRNA are responsible for reduced T3 binding during starvation.
Main Methods:
- Western blot analysis using anti-TR(alpha 1 + beta)antiserum to detect TR proteins.
- Scatchard plot analysis to measure T3-binding capacity (Cmax).
- Study conducted on rat liver following 72 hours of starvation.
Main Results:
- Starvation for 72 hours decreased hepatic TR Cmax to 72.5% of control levels.
- Western blot revealed decreased levels of 47-kd and 55-kd TR proteins to 64% and 66% of control values, respectively.
- Changes in Cmax and TR protein levels correlated with reduced total hepatic nuclear protein concentration.
Conclusions:
- The decrease in T3-binding activity of the TR during starvation is attributed to a reduction in TR protein levels.
- These findings highlight the role of TR protein quantity in regulating thyroid hormone action under metabolic stress.
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