Influence of testosterone on regulation of ODC, antizyme, andN¹-SSAT gene expression in mouse kidney

Abstract

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.

Nuclear and membrane receptor-mediated signalling pathways modulate polyamine biosynthesis and interconversion

“…Translational regulation of AdoMetDC by polyamines, in particular the activating effects of putrescine, has been the subject of intensive investigation [27][28][29]. Our results have demonstrated that polyamine regulation of AdoMetDC activity also occurs in vivo, a finding in line with those reported by other groups [30,31]. Consistent with this notion, in our experimental model of kidney hyperplasia, we found that the activity of AdoMetDC correlated positively with renal putrescine content and negatively with spermine content.…”

“…We have documented that both mRNA content and the activity of SSAT were significantly increased by antifolate CB 3717 (Table 1) and folate injury [15]. In contrast, despite an increase in SSAT mRNA synthesis, a finding consistent with reports from other groups [30,31], SSAT activity was downregulated in the testosterone-induced hypertrophic kidney. Testosterone-induced reduction in SSAT activity (over 40%) was completely abolished by the anti-androgen casodex, implying a role for androgen receptors in the regulation of SSAT [15].…”

Use of suppressive subtractive hybridization and cDNA arrays to discover patterns of altered gene expression in the liver of dihydrotestosterone and 11-ketotestosterone exposed adult male largemouth bass (Micropterus salmoides)

“…This gene was shown to be unaffected by estradiol in mammalian systems by Green et al (1998). Furthermore, Levillain et al (2003) recently showed that SSAT is inducible by testosterone in the male mouse kidney. Further study is needed to explore the potential of SSAT as an androgenic biomarker.…”

Localization and differential expression of arginase II in the kidney of male and female mice

“…Interestingly, in the kidneys of both male and female mice, ODC gene is very sensitive to androgens and is positively regulated by pharmacological and physiological levels of testosterone [39]. Injections of testosterone to mice induce: (1) an upregulation of ODC gene in the three segments of the proximal tubule (PCT, CPST and OSPST) [28], (2) a sharp enhancement in the plasma, renal and urinary level of putrescine [28], and (3) an overexpression of AII gene (manuscript submitted). Interestingly, in the kidneys of testosterone-treated female mice, OAT activity is lower than that of the controls.…”