The reported active metabolite of the pesticide methoxychlor (MC), 2,2,-BIS(P-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), inhibits androgen production by rat ovarian theca interstitial (TI) cells.
Akgul-Y; Derk-RC; Murono-EP
Toxicologist 2006 Mar; 90(1):80
HPTE is reported to be the active metabolite of the pesticide, MC, which is commonly used on agricultural crops and livestock. Following in vivo administration of MC, it is rapidly converted to HPTE by the liver. Both MC and HPTE have been shown to have weak estrogenic and antiandrogenic activities through estrogen and androgen receptors, respectively. Previous in vivo studies in female animals demonstrated decreased progesterone production and no change in estrogens in the blood following exposure to MC. The current in vitro studies examined the effects of HPTE on androgen and progesterone production by cultured ovarian TI cells from immature rats. To isolate TI cells, 24-25 day-old female Sprague-Dawley rats were injected (s.c.) with 20 I.U. of pregnant mare serum gonadotropin. Approximately 48 h following treatment, TI cells were isolated following collagenase digestion of isolated ovarian tissue. TI cells, were cultured in DMEM / F12 medium at 37 0C in a humidified atmosphere of 95 % air and 5 % CO2. Cells were exposed to HPTE for 24 h on the day of plating. The current studies showed that HPTE (0, 10, 25, 50, 100 nM) inhibited testosterone and androstenedione formation in a dose dependent manner with a significant decline to approximately 45 % of control at 100 nM HPTE. Progesterone production was also inhibited with progressive declines to approximately 12 % of control at 100 nM HPTE. Among the steroidogenic enzymes involved in estrogen biosynthesis, HPTE, specifically, inhibited P450 cholesterol side-chain cleavage (P450-SCC) activity in a dose dependent manner. These studies demonstrate that the formation of the main substrates for estrogen production by granulosa cells of the ovarian follicle is inhibited by HPTE.
Pesticides; Pesticides-and-agricultural-chemicals; Agricultural-chemicals; Agriculture; Agricultural-industry; In-vivo-studies; Animals; Animal-studies; In-vitro-studies; Laboratory-animals; Exposure-levels; Exposure-assessment
Disease and Injury: Fertility and Pregnancy Abnormalities
The Toxicologist. Society of Toxicology 45th Annual Meeting and ToxExpo, March 5-9, 2006, San Diego, California