Inverse Shift in Circulating Corticosterone and Leptin Levels Elevates Hypothalamic Deiodinase Type 2 in Fasted Rats

During food deprivation, plasma T4 and T3 levels are decreased. Under this metabolic condition, hypothalamic deiodinase type 2 (D2) activity and mRNA levels are elevated, whereas TRH mRNA levels are suppressed. Systemic T4 administration does not reverse these hypothalamic changes. The mechanism(s) that underlies this paradoxical regulation of D2 during fasting is unknown. We hypothesize that leptin and/or glucocorticoids play a role in these mechanisms, and their interactions may be an important regulator of the hypothalamic-pituitary-thyroid axis. Thus, we assessed the effects of these hormones on D2 activity levels of food-deprived as well as fed animals using enzyme activity measurements. In food-deprived animals, corticosterone replacement reversed the inhibitory effect of adrenalectomy (ADX) on D2 induction, whereas ADX and ADX plus corticosterone replacement did not significantly affect D2 activity levels in rats fed ad libitum. Leptin administration to fed animals did not change D2 activity, where...