Introduction: Androgens are known to play an important role in renal tubular epithelial cell growth, hypertrophy and erythropoetin production, however the exact mechanisms are not clear yet. 5alpha-dihydrotestosterone is synthesized primarily in gonads and skin, and is the most used androgen in studies. However, little is known about testosterone effects in non-gonadal tissues.
Methods: Male Wistar rats aged 810 weeks were orchiectomized and put on a low- or high-salt diet over 5 weeks. In addition they received either placebo, testosterone (1 mg/animal) or 5alpha-dihydrotestosterone (DHT) (1 mg/animal) as daily s.c. injection over 16 days (each group n=6). In additional experiments, rats were treated with mineralocorticoid antagonist spironolactone (50 mg/kg weight per day), which excerts anti-androgenic properties, or androgen receptor antagonist flutamide (30 mg/kg weight per day). Blood and organs were secured after decapitation.
Results: Prostate weight was reduced in ovariectomized rats (20±5 mg); testosterone and DHT treatment significantly increased prostate weight (377±35 and 103±37 mg respectively). Flutamide treatment completely abolished this effect; spironolactone did not show an effect. Testosterone serum concentrations reached 913 ng/ml in testosterone and 0.61 ng/ml in DHT treated rats; testosterone levels were higher in flutamide than in spironolactone treated animals. DHT serum concentrations were 0.81.6 ng/ml in testosterone and 0.51.3 ng/ml in DHT treated rats. No significant differences were observed in estradiol concentrations between the groups. Absolute kidney weight increased significantly in testosterone but not in DHT treated animals. The testosterone effect was reversed by flutamide, but not by spironolactone treatment. In addition, body weight increase was higher in testosterone treated than in control animals, and the effect was significantly diminished by flutamide and by spironolactone treatment.
Conclusions: These results highlight the anabolic effects of testosterone in non-gonadal tissues, especially in kidney epithelial cell growth and hypertrophy. These results indicate the need for further studies of testosterone effects.
03 - 07 May 2008
European Society of Endocrinology