Introduction: There is no difference in blood pressure between boys and girls, but following puberty, blood pressure increases more in men than in women. The higher blood pressure and stronger progression of hypertension in men is associated with a higher risk and mortality for cardiovascular diseases than in women. Androgens are known to play an important role in renal tubular epithelial cell growth, hypertrophy and erythropoetin production and may be important determinants of sex-specific differences in blood pressure. Modulation of epithelial sodium reabsorption through the epithelial sodium channel (ENaC) is an important component in the control of sodium balance. The promoter of the gene encoding for alpha-ENaC harbours an androgen receptor (AR) binding site. We investigated the in vivo effect of testosterone treatment on ENaC expression in rat kidneys.
Methods: Male Wistar rats aged 8-10 weeks were orchiectomized and treated either with a long-lasting testosterone undecanoate (100 mg/kg or 500 mg/kg), or with a 5alpha-dihydrotestosterone preparation (75 mg/pellet per 21-d release) or with placebo (each group n=4). After 14 days the kidneys were removed. RNA was extracted and semi-quantitative PCR was performed using a Typhoon 8600 (molecular dynamics). Relative expressions were normalized by calculating the target gene/18S ratio.
Results: AR was expressed in male rat kidneys and its expression was not influenced by androgen treatment. Renal alpha-ENaC expression was significantly (P<0.01) higher in testosterone (500 mg/kg) than in placebo treated animals. beta- and gamma-ENaC showed a trend towards higher expression in testosterone treated animals. Surprisingly, 5alpha-dihydrotestosterone did not significantly alter the expressions of ENaC subunits or AR.
Conclusions: These data show that alpha-ENaC expression in the rat kidney is regulated by testosterone in vivo. It highlights a potential mechanism explaining the reported gender differences in blood pressure.
01 - 05 Apr 2006
European Society of Endocrinology