Effects of an Endocrine Disruptor on Male Reproductive Organs

A 5-day Hershberger assay, a 20-day pubertal male assay, a one-month oral administration study and a reproductive toxicity study were carried out using an antiandrogenic chemical, flutamide (FL). The effects of FL were as follows: weight decrease in male reproductive organs such as the prostate and seminal vesicles were observed at ≥0.6 mg/kg/day as the most sensitive parameter in the Hershberger assay and the one-month oral administration study. Reduction in number of spermatogenic cells was found at ≥0.6 mg/kg/day as the most sensitive parameter in the 20-day pubertal male assay. A decrease in the anogenital distance was observed at ≥2.5 mg/kg/day as the most sensitive parameter in the reproductive toxicity study. These effects were compared with the reported results of one-month oral administration study of an estrogenic chemical, ethinylestradiol (EE), and an androgenic chemical, methyltestosterone (MT). Differences in the results were as follows: serum hormone levels of LH and testosterone were increased by the FL-treatment, but decreased with EE despite testicular atrophy in all cases. While EE and MT produced atrophic changes in Leydig cells, FL induced their hyperplasia. Thus, different results were obtained regarding serum hormone levels and histopathological changes in Leydig cells with the endocrine disruptor. Attention should be concentrated on these two parameters to clarify and characterize the mechanisms of action of so called endocrine disruptors. (J Toxicol Pathol 2001; 14: 79–82)