The development of genital organs of rats chronically treated with cimetidine showed that the drug may present anti-androgenic activity. Rats were treated i.p. with cimetidine at a dose of 50 mg/kg body weight for 59 days. Accessory sex organ weights, were significantly reduced in the high dose treated groups. A high degree of variability characterized testis histology, with most tubules appearing normal and some tubules (1517%) partially lacking or devoid of germ cells. Morphometry showed that although seminiferous tubule volume was not significantly changed, the volume of peritubular tissue was reduced in the high dose group. There was extensive duplication of the basal lamina, lamina densa in both apparently normal spermatogenic tubules and severely damaged tubules. Apoptotic peritubular myoid cells were also found. Peritubular cells are lost from the testis, it is suggested that the primary event in cimetidine-related damage is targeted to testicular smooth muscle cells. Since no change in serum testosterone levels was verified in cimetidine-treated rats, the authors could not exclude the possibility that besides an antiandrogenic effect, other biochemical factors necessary for normal spermatogenesis could be involved in the testicular alterations. This is the first in vivo-administered toxicant to be described that targets myoid cells, resulting in abnormal spermatogenesis.
01 - 05 Apr 2006
European Society of Endocrinology