title: Selenium-dependent pre- and posttranscriptional mechanisms are responsible for sexual dimorphic expression of selenoproteins in murine tissues.
abstract: Important enzymes for thyroid hormone metabolism, antioxidative defense, and intracellular redox control contain selenocysteine (Sec) in their active centers. Expression of these selenoproteins is tightly controlled, and a sex-specific phenotype is observed on disturbance of selenium (Se) transport in mice. Therefore, we analyzed Se concentrations and expression levels of several selenoproteins including type I iodothyronine deiodinase (Dio1) and glutathione peroxidase (GPx) isozymes in male and female mice. On regular lab chow, serum Se levels were comparable, but serum GPx3 activity was higher in females than males (1.3-fold). Selenoprotein P (SePP) mRNA levels were higher in livers (1.3-fold) and lower in kidneys (to 31%) in female compared with male mice. Orchidectomy alleviated the sex-specific differences in SePP mRNA amounts, indicating modulatory effects of androgens on SePP expression. Female mice expressed higher levels of Dio1 mRNA in kidney (2.6-fold) and liver (1.4-fold) in comparison with male mice. This sexual dimorphic expression of Dio1 mRNA was paralleled by increased Dio1 activity in female kidney (1.8-fold) but not in liver in which males expressed higher Dio1 activity (2.8-fold). Interestingly, Se deficiency decreased Dio1 activity more effectively in males than females, and resulting hepatic enzyme levels were then comparable between the sexes. At the same time, the sex-specific difference of Dio1 activity widened in kidney. Orchidectomy or estradiol treatment of ovariectomized females impacted stronger on renal than hepatic Dio1 expression. Thus, we conclude that Se-dependent posttranscriptional mechanisms are operational that affect either translational efficiency or Dio1 stability in a sex- and tissue-specific manner.
authors.affiliation: Institut fuer Experimentelle Endokrinologie, Charité-Universitaetsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Riese
authors.forename: Marten
authors.initials: M
authors.lastname: Michaelis
authors.forename: Birgit
authors.initials: B
authors.lastname: Mentrup
authors.forename: Franziska
authors.initials: F
authors.lastname: Götz
authors.forename: Josef
authors.initials: J
authors.lastname: Köhrle
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schweizer
authors.forename: Lutz
authors.initials: L
authors.lastname: Schomburg
mesh_terms: D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D007453:Iodide Peroxidase / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009919:Orchiectomy / Q000009:adverse effects; D009928:Organ Specificity; D010052:Ovariectomy / Q000009:adverse effects; D010445:Peptide Elongation Factors / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D012643:Selenium / Q000097:blood / Q000378:metabolism* / Q000502:physiology*; D051140:Selenoproteins / Q000378:metabolism*; D012727:Sex Characteristics
chemical_list: C509159:EFsec protein, mouse; D012739:Gonadal Steroid Hormones; D010445:Peptide Elongation Factors; D051140:Selenoproteins; D007453:Iodide Peroxidase; C507436:selenodeiodinase type 1, mouse; D012643:Selenium