Comparative analysis of thyroid hormone systems in rodents with subterranean lifestyle

Around 250 rodent species inhabit self-constructed burrows. Environmental conditions in these burrows entail risks of overheating, hypoxia, and food shortage, thus many species have evolved low basal metabolism and low body temperature to adapt to these conditions. Measurements of serum thyroid hormone (TH) concentrations in African mole-rats (family: Bathyergidae) have revealed a unique TH phenotype in these animals with very low thyroxine (T4) concentrations paired with rodent-typical 3,3',5-L-triiodothyronine (T3) concentrations, which clearly deviates from the typical mammalian TH pattern. To further characterise the TH system of bathyergid rodents, we analysed thyroid gland morphology and iodide content, TH concentrations, DIO1 and DEHAL1 activity, gene expression, and looked for positively selected sites in proteins involved in TH synthesis in several tissues of two African mole-rat species, the naked mole-rat (Heterocephalus glaber) and the Ansell’s mole-rat (Fukomys anselli). Our results strongly indicate that the unique TH phenotype is already set at the hypothalamus-pituitary-thyroid axis level in both mole-rat species with species-specific differences. In peripheral tissues involved in metabolic rate and thermoregulation, we found differences in TH regulating genes between both species, but both systems correspond with shared physiological traits: low metabolic rate and body temperature. Taken together, the mole-rat TH system is likely to be an upstream regulator of physiological adaptations to the subterranean habitat. Our study emphasises the need to promote research on thyroid hormone biology on a broader spectrum of animals to gain a comprehensive understanding of how these versatile hormones contributed to the evolution of different life histories.