The 5 '-Deiodinases Are Not Essential for the Fasting-Induced Decrease in Circulating Thyroid Hormone Levels in Male Mice: Possible Roles for the Type 3 Deiodinase and Tissue Sequestration of Hormone

摘要

Fasting in rodents is characterized by decreases in serum T-4 and T-3 levels but no compensatory increase in serum TSH level. The types 1 and 2 deiodinases (D1 and D2) are postulated to play key roles in mediating these changes. However, serum T-4 and T-3 levels in fasted 5'-deiodinase-deficient mice decreased by at least the same percentage as that observed in wild-type mice, whereas serum TSH level was unaffected. D3 activity was increased in kidney, muscle, and liver up to 4-fold during fasting, and the mean serum rT(3) level was increased 3-fold in fasted D1-deficient mice, compared with fed animals. In wild-type mice, the tissue contents of T-4 and T-3 in liver, kidney, and muscle were unchanged or increased in fasted animals, and after the administration of [I-125]T-4 or [I-125]T-3, the radioactive content in the majority of tissues from fasted mice was increased 2- or 4-fold, respectively. These findings suggest that the observed fasting-induced reductions in the circulating T-3 and T-4 levels are mediated in part by increased D3 activity and by the sequestration of thyroid hormone and their metabolites in tissues. Studies performed in D3-deficient mice demonstrating a blunting of the fasting-induced decrease in serum T-4 and T-3 levels were consistent with this thesis. Thus, the systemic changes in thyroid hormone economy as a result of acute food deprivation are not dependent on the D1 or D2 but are mediated in part by sequestration of T-4 and T-3 in tissues and their enhanced metabolism by the D3.