Hypothyroidism in hibernating brown bears

Brown bears hibernate throughout half of the year as a survival strategy to reduce energy consumption during prolonged periods with scarcity of food and water. Thyroid hormones are the major endocrine regulators of basal metabolic rate in humans. Therefore, we aimed to determine regulations in serum thyroid hormone levels in hibernation compared to the active state to investigate if these are involved in the adaptions for hibernation. We used electrochemiluminescence immunoassay to quantify total triiodothyronine (T3) and thyroxine (T4) levels in hibernation and active state in paired serum samples from six subadult Scandinavian brown bears. Additionally, we determined regulations in the liver mRNA levels of three major thyroid hormone-binding proteins; thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin, by analysis of previously published grizzly bear RNA sequencing data. We found that bears were hypothyroid when hibernating with T4 levels reduced to less than 44% (P=0.008) and T3 levels reduced to less than 36% (P=0.016) of those measured in the active state. In hibernation, mRNA levels of TBG and albumin increased to 449% (P=0.031) and 121% (P=0.031), respectively, of those measured in the active state. TTR mRNA levels did not change. Hibernating bears are hypothyroid and share physiologic features with hypothyroid humans, including decreased basal metabolic rate, bradycardia, hypothermia, and fatigue. We speculate that decreased thyroid hormone signaling is a key mediator of hibernation physiology in bears. Our fndings shed light on the translational potential of bear hibernation physiology to humans for whom a similar hypometabolic state could be of interest in specifc conditions.