Endocrine Abstracts (2006) 11 P909

The thyroid gland and its selenoenzymes are preferentially supplied in selenium-deficient transgenic mice

L Schomburg1, C Riese1, M Michaelis1, E Griebert1, MO Klein2, R Sapin3, U Schweizer1 & J Koehrle1

1Charité Universitaetsmedizin Berlin, Berlin, Germany; 2Departments of Endocrinology, Centre Hospitalier et Universitaire de Nancy, Nancy, France; 3Institut de Physique Biologique, Unité d’Analyses Endocriniennes, Hopital Civil, Strasbourg, France.

Selenium (Se) is indispensable for enzymatic activities of glutathione peroxidases (GPx) involved in antioxidative defense and deiodinase isozymes (Dio) that control thyroid hormone (TH) action. Se deficiency can impact negatively on thyroid galnd funtioning and TH metabolism and thereby perturb development and metabolism. We have generated Se-deficient mice by genetic inactivation of Selenoprotein P (SePP), the main plasma Se carrier. SePP-KO mice display decreased serum and tissue Se levels and manifest growth defects and neurological abnormalities. Therefore we speculated that the HPT axis and TH metabolism are impaired causing hypothyroidism-like symptoms. Surprisingly, Dio1 and Dio2 were regularly expressed in liver, kidney, thyroid gland and brain, respectively. Thyroid Se levels were also comparable despite strongly reduced Se concentrations in plasma, kidney or even brain of SePP-KO mice. Thyroid glands appeared morphologically normal, thyroid GPx activity was at wild-type levels and serum levels of TSH, or T4 and T3 were at wild-type levels. Pituitary TSHβ transcripts and hepatic Dio1 mRNA levels as markers of intracellular T3 activity were unchanged. During development, cerebellar granule cell migration as a sensitive indicator of local T3 action in brain was undisturbed. Collectively, these findings demonstrate that low levels of serum Se or SePP in the absence of other challenges do not necessarily interfere with the HPT axis. This is surprising with respect to the phenotype of patients with inherited selenoprotein synthesis defects, and indicates a top priority of Se supply to the HTA axis in an otherwise healthy organism.

This work was supported by the Deutsche Krebshilfe and Deutsche Forschungsgemeinschaft, DFG.

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