Atrazine disrupts the hypothalamic control of pituitary-ovarian function

The chloro-S-triazine herbicides (i.e., atrazine, simazine, cyanazine) cons titute the largest group of herbicides sold in the United States. Despite t heir extensive usage, relatively little is known about the possible human-h ealth effects and mechanism(s) of action of these compounds. Previous studi es in our laboratory have shown that the chlorotriazines disrupt the hormon al control of ovarian cycles. Results from these studies led us to hypothes ize that these herbicides disrupt endocrine function primarily through thei r action on the central nervous system. To evaluate this hypothesis, we exa mined the estrogen-induced surges of luteinizing hormone (LH) and prolactin in ovariectomized Sprague-Dawley (SD) and Long-Evans hooded (LE) rats trea ted with atrazine (50-300 mg/kg/day, by gavage) for 1, 3, or 21 days. One d ose of atrazine (300 mg/kg) suppressed the LH and prolactin surge in ovarie ctomized LE, but not SD female rats. Atrazine (300 mg/kg) administered to i ntact LE females on the day of vaginal proestrus was without effect on ovul ation but did induce a pseudopregnancy in 7 of 9 females. Three daily doses of atrazine suppressed the estrogen-induced LH and prolactin surges in ova riectomized LE females in a dose-dependent manner, but this same treatment was without effect on serum LH and prolactin in SD females. The estrogen-in duced surges of both pituitary hormones were suppressed by atrazine (75-300 mg/kg/day) in a dose-dependent manner in females of both strains evaluated after 21 days of treatment. Three experiments were then performed to deter mine whether the brain, pituitary, or both organs were the target sites for the chlorotriazines, These included examination of the ability of (1) the pituitary lactotrophs to secrete prolactin, using hypophyosectomized female s bearing pituitary autotransplants (ectopic pituitaries); (2) the syntheti c gonadotropin-releasing hormone (GnRH) to induce LH secretion in females t reated with high concentrations of atrazine for 3 days; and (3) atrazine (a dministered in vivo or in vitro) to suppress LH and prolactin secretion fro m pituitaries, using a flow-through perifusion procedure, In conclusion, th e results of these studies demonstrate that atrazine alters LH and prolacti n serum levels in the LE and SD female rats by altering the hypothalamic co ntrol of these hormones. In this regard, the LE female appeared to be more sensitive to the hormone suppressive effects of atrazine, as indicated by t he decreases observed on treatment-day 3. These experiments support the hyp othesis that the effect of atrazine on LH and prolactin secretion is mediat ed via a hypothalamic site of action.