ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P353

Impaired Se metabolism provokes gender-specific growth defects in mice

Kostja Renko1, Alexandra Chadt2, Marten Michaelis1, Ulrich Schweizer1, Hadi Al-Hasani2, Josef Köhrle1 & Lutz Schomburg1


1Institut für Experimentelle Endokrinologie, Charité Universitätsmedizin Berlin, Berlin, Germany; 2Deutsches Institut für Ernährungsforschung (DIfE), Potsdam, Germany.


Background: Selenoproteins are involved in oxidative stress defence, cell signalling and hormone metabolism. Accordingly, impairment of selenium (Se) metabolism or transport results in a complex phenotype as exemplified in selenoprotein P knockout mice (SePP-KO). This mouse model is characterized by a disrupted metabolism of Se resulting in neurological and growth defects. Hypothesis: Se impairs regular tissue development by modifying growth signal biosynthesis, anabolic responses or oxidative stress levels within endocrine glands or target tissues.

Methods: Male and female wild-type, heterozygous and SePP-KO mice were raised on regular chow with defined Se-content. The expression of growth-relevant genes was studied in target tissues by qPCR and Northernblot analyses at 35 or 42 days of age. Serum markers like IGF-1 and IGF-BPs were determined by ELISA.

Results: Male SePP-KO mice displayed progressively reduced body weight gain starting two weeks after weaning. In contrast, female SePP-KO mice had a reduced bodyweight right from the beginning, but body mass differences diverged not further during the observational period. Significant differences in mRNA levels (57% reduction versus wild-type, P<0.01) and IGF1 serum levels (23% reduction versus wild-type, P<0.05) were exclusively observed in males. These findings underline the importance of Se for regular growth and health status and highlight medically important gender-differences in Se metabolism.

Conclusion: Se metabolism, Se status and transport are involved in tissue growth and body mass regulation. Our findings on the impact of gender on the SePP-KO phenotype may help to understand sex-specific effects of Se-supplementation in the clinics during disease prevention programs and therapeutical trials.

Supported by Deutsche Krebshilfe (10-1792 SchoII) and DFG (SCHO 849/2-1).

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