Veränderte Thyroidhormonphysiologie in Nagetieren – eine konvergente Adaptation an strenge Umweltbedingungen
Zusammenfassung der Projektergebnisse
Thyroid hormones (THs) play a central role in both, physiology and pathophysiology of animals, but research on THs is dominated by biomedical research focusing on pathophysiology. Previously, it has been reported that some vertebrate species regulate TH signaling in conjunction with seasonal behaviors such as reproduction, migration, and hibernation. In our project, we aimed at extending this comparative view on the function of THs in animal physiology and the evolution of different life histories by focusing on a group of rodents, so called subterranean rodents that inhabit self-dug burrow systems. We followed mainly three research lines to identify proximate (mechanistic) and ultimate (evolutionary) mechanisms of the TH system of subterranean rodents. First, we characterized the TH system at the molecular level of two subterranean African rodent species, the naked mole-rat (Heterocephalus glaber) and the Ansell’s mole-rat (Fukomys anselli) and compared it with the laboratory mouse (Mus musculus), a well-characterized model in thyroid hormone research, which lives above-ground. Compared to mice, both subterranean rodent species exhibit a unique TH phenotype, which also differed from the typical mammalian pattern in major aspects. While concentrations of the prohormone thyroxine (T4) were exceptionally low, more similar to those of poikilothermic reptiles than mammals, concentrations of the biologicallyactive triiodothyronine (T3) were similar to those found in other mammalian species. At the tissue level, we found that the TH phenotype in naked mole-rats and Ansell’s mole-rats is differentially regulated. Although these two species belong to the same family (Bathyergidae), the naked mole-rat diverged from other African mole-rats approximately 31 million years ago. Thus, these two species underwent a long period of independent evolution while living in similar habitats, suggesting that the mole-rat’s TH system represents a convergent adaptation to the subterranean lifestyle. Second, we treated Ansell’s mole-rats with T4 to investigate implications of the unique TH system for a life underground. Analysis of treatment effects on metabolic rate and thermoregulation provided strong evidence that the TH system of mole-rats is an upstream regulator of physiological adaptations crucial for a life underground. Third, we established a near-natural experimental setting to keep Ansell’s mole-rats under hypoxic and hypercapnic conditions to resemble atmospheric conditions found in subterranean burrow systems. We found that chronic hypoxia and hypercapnia decreased concentrations of the free T3 (fT3), which can enter target cells to modulate gene expression, suggesting that TH signaling is downregulated under hypoxic/hypercapnic conditions. Furthermore, erythropoiesis was downregulated, which resulted in a reduced number of erythrocytes and hemoglobin. Taken together, this project has promoted our understanding of how African mole-rats have evolved a subterranean lifestyle.
Projektbezogene Publikationen (Auswahl)
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Comparative analysis of thyroid hormone systems in rodents with subterranean lifestyle. Scientific Reports, 13(1).
Gerhardt, Patricia; Begall, Sabine; Frädrich, Caroline; Renko, Kostja; Hildebrandt, Thomas B.; Holtze, Susanne; Heinrich, Alexandra; Sahm, Arne; Meci, Xheni; Köhrle, Josef; Rijntjes, Eddy & Henning, Yoshiyuki
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Hypoxic and hypercapnic burrow conditions lead to downregulation of free triiodothyronine and hematocrit in Ansell’s mole-rats (Fukomys anselli). Journal of Comparative Physiology B, 194(1), 33-40.
Henning, Yoshiyuki; Adam, Kamilla; Gerhardt, Patricia & Begall, Sabine
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Low thyroxine serves as an upstream regulator of ecophysiological adaptations in Ansell’s mole-rats. Frontiers in Endocrinology, 15.
Gerhardt, Patricia; Begall, Sabine; Frädrich, Caroline; Renko, Kostja; Heinrich, Alexandra; Köhrle, Josef & Henning, Yoshiyuki
