The influence of sex hormones on renal osteopontin expression and urinary constituents in experimental urolithiasis

Purpose: To our knowledge the influence of sex hormones on urinary stone formation remains undetermined. We investigated the effect of castration on urinary lithogenic factors and renal osteopontin expression in rats previously treated with ethylene glycol. Materials and Methods: Sprague-Dawley rats were divided normal males, castrated males, males with 2 weeks of 0.75% ethylene glycol treatment, castrated males with 2 weeks of 0.75% ethylene glycol treatment, normal females, castrated females, females with 2 weeks of 0.75% ethylene glycol treatment and castrated females with 2 weeks of 0.75% ethylene glycol treatment. We analyzed 24-hour urine samples for urinary constituents, such as calcium, oxalate, citrate, uric acid, phosphate, magnesium, sodium, potassium and creatinine. The kidneys were examined for osteopontin expression by Northern blot analysis and for crystal deposition by histological examination. Results: In intact male rats calcium and citrate excretion decreased and oxalate excretion increased significantly after ethylene glycol treatment. Castrated male rats with ethylene glycol had greater calcium and less oxalate excretion than male intact rats with ethylene glycol. In intact female rats uric acid excretion decreased and only calcium excretion increased significantly after ethylene glycol treatment. Castrated female rats with ethylene glycol excreted significantly more oxalate and less calcium than intact female rats with ethylene glycol. Renal osteopontin expression was the same in male intact and castrated rats, and in female intact and castrated rats. In males with ethylene glycol expression was stronger in castrated than in intact rats. In females with ethylene glycol expression was weaker in castrated than in intact rats. No crystal deposits were found in the kidneys in any group. Conclusions: Testosterone appears to promote stone formation by suppressing osteopontin expression in the kidneys and increasing urinary oxalate excretion. Estrogen appears to inhibit stone formation by increasing osteopontin expression in the kidneys and decreasing urinary oxalate excretion.