Inhibitory effects of female sex hormones on urinary stone formation in rats

Background. The effects of female sex hormones on urinary stone formation are not known. This study was conducted to investigate the effects of these hormones on stone formation by using an ethylene glycol (EG) and vitamin D-induced rat urolithiasis model. Methods. Adult female Wistar rats were fed the same diet for four weeks and were then divided into four groups (N = 10 each). One group was administered 0.5 mi of olive oil three times per week for four weeks as a control. The other three groups were administered 0.5 mu g of vitamin D-3 and 0.5 mi of 5% EG three times per week for four weeks. The rats in two of these three groups were oophorectomized, and the rats of the remaining group underwent a sham operation on the day before the start of the four-week treatment period. One of the two oophorectomized groups was then administered a supplementation of female sex hormones (0.1 mg of estrogen and 2.5 mg of progesterone 3 times per week for 4 weeks). On the first day of the fifth week of the experimental period, the degree of crystal deposition was determined histologically, and the calcium content in renal tissue was measured. We also investigated the level of osteopontin (OPN) mRNA in renal tissues by Northern blot analysis. OPN is a matrix protein thought to be a promoter of stone formation. Results. The urinary oxalate excretion, crystal deposition and calcium content in renal tissue and the expression of OPN-mRNA were greater in the oophorectomized rats compared with the controls, and the same parameters were inhibited by the female sex hormone supplementation. Conclusions. These results suggest that female sex hormones can inhibit renal crystal deposition in EG-treated rats by suppressing the urinary oxalate excretion and the expression of OPN.