Effects of atrazine and its withdrawal on gonadotropin-releasing hormone neuroendocrine function in the adult female Wistar rat.
High doses of the commonly used herbicide atrazine have been shown to suppress luteinizing hormone (LH) release. To determine whether atrazine alters the function of gonadotropin-releasing hormone (GnRH) neurons, we examined the effects of atrazine on GnRH neuronal activation and the subsequent release of LH normally associated with ovulation. Ovariectomized adult Wistar rats were administered atrazine (50, 100, or 200 mg/kg of body weight daily by gavage) or vehicle for 4 days. Animals were primed with estrogen and progesterone to induce an evening LH surge. Blood samples were obtained over the afternoon and evening using an indwelling right atrial cannula, and plasma was assayed for LH and FSH. Another cohort of animals was transcardially perfused in the afternoon to examine GnRH activation using FOS immunoreactivity. Results of these studies show that 4-day treatment with atrazine resulted in a significant reduction in the magnitude of the LH and FSH surges, and this corresponds to a decrease in GnRH neurons expressing FOS immunoreactivity. To determine if the effects of atrazine were long lasting, additional studies were performed examining LH levels and GnRH activation 2 days and 4 days after atrazine withdrawal. Within 4 days (but not 2 days) after cessation of atrazine treatment, measures of hypothalamic-pituitary-gonadal (HPG) activation returned to normal. These data indicate that atrazine affects neuroendocrine function in the female rat by actions at the level of the GnRH neuron and that the acute effects of high doses of atrazine can be reversed within 4 days after withdrawal of treatment.
Foradori
Chad D
CD
Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA. chad.foradori@arizona.edu
Hinds
Laura R
LR
Hanneman
William H
WH
Handa
Robert J
RJ
D000704:Analysis of Variance; D000818:Animals; D001280:Atrazine / Q000008:administration & dosage*; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006540:Herbicides / Q000008:administration & dosage; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D007986:Luteinizing Hormone / Q000097:blood; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function
D006540:Herbicides; D016760:Proto-Oncogene Proteins c-fos; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D001280:Atrazine