Glucose infusion increases mRNA expression of deiodinase 1 & 2, and thyroid hormone receptor β‐1 in a fasting‐adapted mammal (1101.12)

Abstract

Food deprivation in mammals is typically associated with reduced glucose, thyroid hormone (TH) concentrations and deiodinase (DI) content and activity to suppress metabolism. However, in prolong‐fasted, metabolically active elephant seal pups, the hypothalamic‐pituitary‐thyroid axis (HPT axis), which is responsible for the production of TH, is up‐regulated. The functional relevance of this apparent paradox is unknown and demonstrates variability in the regulation of TH levels, metabolism and function in food‐deprived mammals. To address our hypothesis that increased glucose increases peripheral TH receptor beta‐1 (THrβ‐1) mRNA expression and content in prolong‐fasted pups, we assessed the cellular TH‐mediated response to a glucose challenge by measuring TH profiles during a glucose tolerance test (GTT) and comparing the changes in profiles in early and late fasted pups. THrβ‐1 mRNA expression increased 59% ± 24 and 336% ± 95 by the 60 and 120 minute mark, respectively. Protein expression of THrβ‐1 also increased during the GTT, 40% ± 4 and 80% ± 23 at 60 and 120 minutes, respectively. mRNA expression of DI1 and DI2 increased by the 120 minute time point, 100% ± 34 and 400% ± 63, respectively. The data suggests that cellular TH pathways are responsive to changes in glucose, which in turn maybe regulated by TH. This suggests that the HPT axis is active and functional during prolonged food‐deprivation in metabolically and physically active mammals.Grant Funding Source: Supported by NIH/NHLBI 442606‐RO‐29013