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Submitted on September 8, 2004
Accepted on November 3, 2004
Université Claude Bernard, Faculté de Médecine Lyon R.T.H. Laennec, Laboratoire de Physiopathologie Métabolique et Rénale, Institut National de la Santé et de la Recherche Médicale (INSERM) U 499, 7, rue G. Paradin, 69372 Lyon Cedex 08; Université Claude Bernard, Centre de Génétique Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5534, 69622 Villeurbanne; France; Hospices Civils de Lyon: Service de Radioanalyse, Centre de Médecine Nucléaire, Hôpital Neuro-Cardiologique and INSERM EMR 0322, 69394 Lyon Cedex 03, France
* To whom correspondence should be addressed. E-mail: Olivier.Levillain{at}laennec.univ-lyon1.fr.
The enzymes ornithine aminotransferase (OAT) and ornithine decarboxylase (ODC) share L-ornithine as a common substrate and arginase II produce this amino acid. In the murine kidney, testosterone induced ODC gene expression and polyamine production but it is unknown how OAT gene is expressed under androgen treatment. These experiments were designed to study the influence of testosterone on the renal expression of OAT gene. Pharmacological and physiological doses of testosterone were injected to female and castrated male mice. Total RNA and soluble proteins extracted from whole kidneys were analyzed by Northern and Western blots, respectively. The results clearly indicate that pharmacological doses of testosterone simultaneously down-regulated the level of OAT protein and up-regulated the expression of arginase II and ODC genes. Variations of the levels of OAT protein and arginase II mRNA and protein were strongly correlated with testosteronemia. Orchidectomy increased the renal level of OAT protein, decreased that of ODC and arginase II. These effects were reversed by injecting a physiological dose of testosterone to castrated male mice. In conclusion, OAT and ODC genes are inversely regulated by testosterone in the mouse kidney. Consequently, in kidneys of testosterone-treated mice, L-arginine-derived ornithine produced by arginase II might be preferentially used by ODC for putrescine production rather than by OAT. This metabolic fate of L-ornithine was facilitated by decreasing OAT gene expression. In contrast, in female and castrated male mice devoided of testosterone, OAT gene is highly expressed and L-ornithine is converted into L-glutamate
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