In vivo exposure of young, adult rats to methoxychlor (M) reduces serum testosterone (T) levels, basal Leydig cell (LC) T formation, LC cytochrome P450 cholesterol side-chain cleavage (P450SCC) activity and serum dehydroepiandrosterone (DHEA) levels.
Murono-EP; Derk-RC; Castranova-V
Toxicologist 2004 Mar; 78(S-1):188
M is a pesticide developed as a replacement for dichlorodiphenyltrichloroethane (DDT). Although its metabolite, 2, 2-bis(p-hydroxyphenyl)-1, 1, 1-trichloroethane (HPTE), is thought to be the active compound, both M and HPTE have been reported to exhibit weak estrogenic and/or antiandrogenic activities and thereby produce adverse reproductive effects in rodents. In the current studies young adult male rats (at least 11 animals per each treatment group) were gavaged once daily between days 54-60 days of age with 0, 5, 40 or 200 mg M/kg body weight in corn oil. Animals were sacrificed approximately 24 h after the last exposure to assess the effects of M on LC steroidogenic competence. Serum T levels declined from 4.40 +/- 0.52 ng/ml (control) to 1.82 +/- 0.27 ng/ml at the 200 mg/kg dose. Similarly, both wet and expressed seminal vesicle weights declined to 44 and 60% of control, respectively, at the highest exposure dose. However, serum LH and FSH levels were unaffected by M. In addition, testicular LC isolated from exposed animals produced less T under basal conditions following a 4 h incubation period (2.20 +/- 0.13 ng T/4 h/10^5 cells in LC from 200 mg/kg exposed animals vs 4.50 +/- 0.31 ng/4 h/10^5 cells in control cells). Also, P450scc activity of isolated LC declined from 20.44 +/- 0.92 ng side-chain/h/10^5 cells (control) to 16.10 +/- 1.29 and 10.15 +/- 0.98 ng/h/10^5 cells in LC from animals exposed to 40 and 200 mg/kg M, respectively. Although serum corticosterone levels were unaffected by M, serum DHEA levels declined from 0.11 +/- 0.01 ng/ml (control) to 0.05 +/- 0.01 ng/ml in 200 mg/kg exposed animals. Whether this decline in DHEA represents adrenal or LC androgen remains to be determined. These studies suggest that in vivo exposure of M to young adult male rats directly reduces LC T formation and that this decline is due to inhibition of LC P450scc activity.
In-vivo-studies; Exposure-levels; Laboratory-animals; Animals; Animal-studies; Pesticides; Reproductive-system-disorders; Reproductive-effects
72-43-5; 50-29-3; 71-55-6
Disease and Injury: Fertility and Pregnancy Abnormalities
The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland