A REVIEW OF DRUG-INDUCED LEYDIG-CELL HYPERPLASIA AND NEOPLASIA IN THERAT AND SOME COMPARISONS WITH MAN

This paper describes control of normal Leydig cell function and testos terone production. The macroscopic and histopathological appearances o f spontaneous Leydig cell hyperplasias and tumors (LCT) in the rat are reviewed together with their incidence and hormonal status. Drugs whi ch induce LCTs in chronic studies are discussed and include busereline , carbamazepine, cimetidine, finasteride, flutamide, gemfibrozil, hist relin, hydralazine, indomethacin, isradipine, lactitol, leuprolide, me tronidazole, mesulergine, nafarelin, norprolac and vidarabine. The kno wn mechanisms of LCT induction in the rat are reviewed together with o ther possible etiological factors. The incidence, clinical picture and etiological factors of LCTs in man are also surveyed. Hormone product ion in Leydig cells and LCTs in rats and man are compared. Differences between the two species are considered, particularly with regard to L eydig cell control mechanisms, The paper concludes that drug-induced L CTs in rats are most probably not predictive for man and their occurre nce has little relevance in human safety assessment.