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In vivo exposure of prepubertal rats to methoxychlor (M) inhibits ex vivo Leydig cell (LC) basal and human chorionic gonadotropin (HCG)- stimulated testosterone (T) formation.
Murono EP; Derk RC
Toxicologist 2005 Mar; 84(Suppl 1):112
M is pesticide which has been used as a replacement for DDT. Its active metabolite is reported to be 2, 2-bis(p-hydroxyphenyl)-1, 1, 1-trichloroethane (HPTE), and both M and HPTE exhibit weak estrogenic and/or antiandrogenic activities and have adverse reproductive effects on animals. In the current studies, prepubertal male rats (12 animals per treatment group) were gavaged once daily between 24-30 days of age with 0, 5, 40 or 200 mg/kg body weight of M in corn oil to evaluate whether LC from immature rats are sensitive to M. Animals were sacrificed approximately 24 h after the last exposure, and LC were isolated by density-gradient centrifugation of dispersed testes. Ex vivo LC T formation was measured after 4 h of incubation under basal conditions and following exposure to 10 mIU/ml hCG. In addition, because immature LC express high 5a-reductase (5a-R) activity, which causes the majority of synthesized T to be metabolized to dihydrotestosterone and its hydroxylated metabolites, a 5a-R inhibitor was added to assess total T biosynthetic capacity. Final body weights of M-treated animals were no different than control; however, testes and seminal vesicle weights declined significantly to 81 and 69% of control, respectively, in animals exposed to 200 mg/kg M. Ex vivo LC T formation over 4 h under basal conditions declined significantly to 29% of control at the highest dose of M. A similar pattern of decline in T was observed when LC were incubated with a 5a-R inhibitor, but T levels were >30-fold higher. LC T formation following exposure to hCG for 4 h declined significantly to 34% of control in animals exposed to 200 mg/kg M, and a similar pattern of T decline was observed when LC were incubated with a 5á-R inhibitor, except T levels were approximately 60-fold higher. Of interest, serum T, LH and FSH levels were unaffected by M. These results suggest that LC from immature rats are highly sensitive to the inhibitive effects of M.
Laboratory-animals; Animals; Animal-studies; In-vivo-studies; Exposure-levels; Exposure-assessment; Pesticides; Reproductive-effects; Pesticides-and-agricultural-chemicals; Insecticides; Metabolites; Metabolic-study
Disease and Injury: Fertility and Pregnancy Abnormalities
The Toxicologist. Society of Toxicology 44th Annual Meeting and ToxExpo, March 6-10, 2005, New Orleans, Louisiana
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Content source: National Institute for Occupational Safety and Health Education and Information Division