Hepatic deiodinase activity is dispensable for the maintenance of normal circulating thyroid hormone levels in mice.
Thyroid hormone (TH) homeostasis depends on peripheral activation and inactivation of iodothyronines by selenoenzymes of the deiodinase (Dio) family. We genetically inactivated hepatic selenoenzyme expression, including Dio1, in order to determine the contribution of hepatic Dio to circulating TH levels. Serum levels of TSH, total T(4), and total T(3) were not different from controls. We measured Dio1 and Dio2 in kidney, skeletal muscle, heart, brown adipose tissue, and brain, but did not find compensatory up-regulation in these tissues. Finally, we determined expression in the liver of the following T(3) target genes: Spot14, alpha-glycerophosphate dehydrogenase (alphaGPD), and malic enzyme (ME). On the transcript level, both Spot14 and alphaGPD were reduced in Dio-deficient liver to about 60-70% of controls. However, mRNA and activity of ME were significantly increased in the same mice. Together, our results indicate that hepatic Dio1 activity is not absolutely required to sustain the euthyroid state in mice.
Streckfuss
Florian
F
Neurobiology of Selenium, Neuroscience Research Center, Charité Universitätsmedizin, Berlin, Germany.
Hamann
Inka
I
Schomburg
Lutz
L
Michaelis
Marten
M
Sapin
Remy
R
Klein
Marc O
MO
Köhrle
Josef
J
Schweizer
Ulrich
U
D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D007453:Iodide Peroxidase / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008291:Malate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013963:Thyroid Hormones / Q000097:blood*; D013972:Thyrotropin / Q000097:blood; D014018:Tissue Distribution; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C120687:Dido protein, mouse; D009687:Nuclear Proteins; D012333:RNA, Messenger; C501477:Thrsp protein, mouse; D013963:Thyroid Hormones; D014157:Transcription Factors; D013972:Thyrotropin; D005993:Glycerolphosphate Dehydrogenase; D008291:Malate Dehydrogenase; C109812:iodothyronine deiodinase type I; D007453:Iodide Peroxidase