Temperature-responsive release of thyroxine and its environmental adaptation in Australians.
The hormone thyroxine that regulates mammalian metabolism is carried and stored in the blood by thyroxine-binding globulin (TBG). We demonstrate here that the release of thyroxine from TBG occurs by a temperature-sensitive mechanism and show how this will provide a homoeostatic adjustment of the concentration of thyroxine to match metabolic needs, as with the hypothermia and torpor of small animals. In humans, a rise in temperature, as in infections, will trigger an accelerated release of thyroxine, resulting in a predictable 23% increase in the concentration of free thyroxine at 39°C. The in vivo relevance of this fever-response is affirmed in an environmental adaptation in aboriginal Australians. We show how two mutations incorporated in their TBG interact in a way that will halve the surge in thyroxine release, and hence the boost in metabolic rate that would otherwise occur as body temperatures exceed 37°C. The overall findings open insights into physiological changes that accompany variations in body temperature, as notably in fevers.
Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, , Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, UK, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education of China, School of Medicine, Shanghai JiaoTong University, , No. 280, Shanghai 200025, People's Republic of China.
Xiaoqiang
X
Qi
Wee Lee
WL
Chan
Randy J
RJ
Read
Aiwu
A
Zhou
Robin W
RW
Carrell
D000222:Adaptation, Physiological; D000818:Animals; D001831:Body Temperature; D005334:Fever / Q000097:blood / Q000378:metabolism; D006801:Humans; D007035:Hypothermia / Q000097:blood / Q000378:metabolism; D008322:Mammals / Q000097:blood / Q000378:metabolism / Q000502:physiology; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D013974:Thyroxine / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D056825:Thyroxine-Binding Globulin / Q000235:genetics / Q000378:metabolism
D056825:Thyroxine-Binding Globulin; D013974:Thyroxine
aboriginal Australian; febrile convulsions; hibernation; hypothermia; thyroxine; thyroxine-binding globulin