Orchidectomy Upregulates While Testosterone Treatment Downregulates the Expression of Ornithine Aminotransferase Gene in the Mouse Kidney

Ornithine aminotransferase (L-ornithine: 2-oxoacid aminotransferase, OAT, EC 2.6.1.13) plays crucial physiological roles in amino acid metabolism because this enzyme is at the crossroad of several pathways including those of L-arginine, L-ornithine, L-glutamate, Lglutamine, and L-proline. Specifically, OAT catalyzes the transamination of L-ornithine in the presence of α-ketoglutarate to produce one molecule of L-glutamate and the unstable compound glutamate-γ-semialdehyde that is spontaneously converted into ∆1-pyrroline-5carboxylate. This latter molecule is further metabolized by the enzyme pyrroline-5carboxylate dehydrogenase into a second molecule of L-glutamate (Wakabayashi, 2004). The enzyme is expressed in many mammalian tissues including the liver, the kidney, and the intestine which exhibit the highest OAT activities (Peraino & Pitot, 1963; Herzfeld & Knox, 1968; Sanada et al., 1970; Kasahara et al., 1986; Alonso & Rubio, 1989; Levillain et al., 2007; Ventura et al., 2009). These enzymes may not only display diverse tissue-specific physiological roles, but demonstrate marked sexual differences in expression and activity. In rat kidneys, estrogen dramatically increased the expression of OAT and is responsible for the higher levels of OAT in female than in male rat kidney (Herzfeld & Knox, 1968; Lyons & Pitot, 1977; Mueckler & Pitot, 1983; Mueckler et al., 1984; Levillain et al., 2004). The presence of thyroid hormone is required for estrogen induction. These hormones exert a synergistic effect on the expression of OAT gene (Mueckler & Pitot, 1983). The expression of OAT gene during the rat postnatal development strongly supports the sexual dimorphism of OAT in kidney, but not in liver (Herzfeld & Knox, 1968; Herzfeld & Greengard, 1969). Taken together, the expression of OAT gene in the female rat kidney is naturally upregulated in the presence of estrogen. The expression of OAT gene in the mouse kidney has been reported by different authors who independently measured OAT mRNA and protein levels or OAT activity (Alonso & Rubio, 1989; Natesan & Reddy, 2001; Yu et al., 2003; Levillain et al., 2005; ManteuffelCymborowska et al., 2005; Levillain et al., 2007; Ventura et al., 2009). Strong evidences