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Influence of testosterone on regulation of ODC, antizyme, and N¹-SSAT gene expression in mouse kidney

¹Laboratoire de Physiopathologie Métabolique et Rénale, Faculté de Médecine Lyon R. T. H. Laënnec, Institut National de la Santé et de la Recherche Médicale, Unite 499, 69372 Lyon Cedex 08; ²Centre de Génétique Moléculaire et Cellulaire-Unité Mixte de Recherche 5534, 69622 Villeurbanne; ³Laboratoire Neurogenèse et Morphogenèse dans le Développement et chez l'Adulte, 13288 Marseille Cedex 9; and ⁴Neuroscience et Systèmes Sensoriels, Université Claude Bernard-Centre National de la Recherche Scientifique-Unité Mixte de Recherche 5020, 69366 Lyon Cedex 07, France

Submitted 15 November 2002 ; accepted in final form 17 April 2003

Polyamines are involved in the control of the cell cycle and cell growth. In murine kidney, testosterone enhances gene expression of ornithine decarboxylase (ODC), the first enzyme in polyamine biosynthesis. In this study, we document the time course effect of testosterone on 1) gene expression of ODC, antizyme 1 (AZ1), and spermidine/spermine-N¹-acetyltransferase (N¹-SSAT); 2) ODC activity in proximal convoluted tubules (PCT) and cortical proximal straight tubules (CPST); and 3) renal polyamine levels. Female mice were treated with testosterone for a period of 1, 2, 3, and 5 consecutive days. ODC gene expression was extremely low in kidneys of untreated female mice compared with that of males. Consequently, the renal putrescine level was sevenfold lower in females than in males, whereas spermidine and spermine levels did not differ between sexes. In female kidneys, testosterone treatment sharply increased ODC mRNA and protein levels as well as ODC activity. Testosterone increased the expression of ODC in PCT and CPST over different time courses, which suggests that ODC activity is differentially regulated in distinct tubules. The expression of AZ1 and N¹-SSAT mRNA was similar in male and female mouse kidneys. Testosterone treatment enhanced AZ1 and N¹-SSAT mRNA levels in a time-dependent manner by unknown molecular mechanisms. Putrescine and spermidine levels increased after testosterone treatment in female kidneys. Surprisingly, although ODC protein and activity were undetectable in female kidneys, the levels of AZ1 mRNA and protein were similar to those in males. Therefore, one may propose that ODC protein could be continuously degraded by AZ1 in female kidneys.

isolated tubules; proximal tubule; permeabilized tubules; gene expression regulation

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