Effects of cyclosporin A on sex hormone and estrogen receptor in male rat with special reference to cyclosporin A-induced osteoporosis

The mechanisms of high turnover bone loss induced by Cyclosporin A (CsA) ar e not clearly understood. Deficiencies in sex hormones result in high turno ver osteoporosis, and not only androgen bur also estrogen plays an importan t role in maintaining bone mass in men. To study whether or not there are a ny changes in the levels of sex hormones, aromatization, and the expression of estrogen receptors in CsA-induced osteoporosis, we treated 39 rats with vehicle, low-dose CsA (5 mg/kg) and high dose CsA (15 mg/kg) for 28 days, and measured sex hormone levels by radioimmunoassay. Aromatase activities i n ROS cells and 3T3-L1 cells were determined by measuring the conversion ra te of H-3-androstenedione into H-3-estrone. ER and ER mRNA were measured by competitive RT-PCR in collected marrow cells and ROS cells. The levels of free testosterone in the serum in low-dose CsA-treated rats were unchanged, but the levels were significantly decreased in those treated with high-dos e CsA as previously reported. The levels of total estradiol in the serum we re significantly increased in the low-dose CsA-treated group (5 mg/kg) and were comparable to levels of the control group in the high-dose CsA-treated group (15 mg/kg). CsA increased the conversion of H-3-androstenedione ro H -3-estrone in ROS cells, but not in 3T3-L1 cells. Meanwhile, CsA treatment did not change the rates of ER or ER mRNA expression in ROS cells or in col lected bone marrow cells. In conclusion, CsA treatment decreased the level of free testosterone in the serum, but did not decrease the level of serum estradiol by enhancing aromatization. High-turnover osteoporosis induced by clinical dosage CsA treatment may not be caused by lowering the levels of circulating estrogen or by decreasing the expression of estrogen receptors.