Gender-specific differences in the expression of deiodinase I (Dio1) in mammals
C Riese, U Schweizer, J Köhrle & L Schomburg
Selenium (Se) represents an essential trace element and acts as catalytic entity in thyroid hormone deiodinases (Dio), glutathione peroxidases or thioredoxin reductases. Se-deficiencies worsen a variety of conditions of which some display a sex-bias, including certain forms of cancer, autoimmune- and infectious diseases. Using C57BI/6 mice as model organism, we determined enzymatic activities and transcript levels of certain selenoproteins in various tissues. mRNA levels of the Se transporter (SePP) were higher in female liver, but lower in kidney compared to male littermates, but serum Se levels were comparable. Dio1 activities of female mice were lower in liver (to 60% of male values), but higher in kidney (14.2±3.4 versus 7.7±2.1 pmol/(mg*min)). Corresponding Dio1 transcript levels were similarly different in kidney of these mice (higher in females by 2-fold compared to male littermates). Unexpectedly, Dio1 transcript levels were also significantly higher in livers of females compared to male littermates (by 1,6-fold). This difference is mirror-image to the measured activities in livers, and argues for differential translational efficiencies of Dio1 mRNA between the sexes, or for different half-lives of the Dio1 protein. Since there are no data supporting the latter theory at present, and because of the similar Se serum levels, we assume that the female hepatic selenoprotein biosynthesis machinery translates Dio1 and SePP mRNA less efficiently.
Therefore, it is unfortunate for endocrinologists, neurologists and oncologists, that large-scale Se supplementation studies Se in the USA (e.g. SELECT, 180 Mio US$ for 712 years and 32400 participants) focus only on male patients.
Supported by the German Cancer Aid and the German Research Foundation (DFG).