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Toxicol Ind Health

Title:		The estrogenic and antiandrogenic pesticide methoxychlor alters the reproductive tract and behavior without affecting pituitary size or LH and prolactin secretion in male rats
Author(s):		Gray LE; Ostby J; Cooper RL; Kelce WR;
Address:		"Endocrinology Branch, United States Environmental Protection Agency, Research Triangle Park, NC 27111, USA. gray.earl@epamail.epa.gov"
Journal Title:		Toxicol Ind Health
Year:		1999
Volume:		15
Issue:		1-Feb
Page Number:		37 - 47
DOI:		10.1177/074823379901500105
ISSN/ISBN:		0748-2337 (Print) 0748-2337 (Linking)
Abstract:		"This study was designed to determine if long-term exposure to high doses of methoxychlor (M) would alter pituitary or testicular endocrine functions in either an estrogenic or antiandrogenic manner. Weanling male Long-Evans hooded rats were dosed daily with M (po) at 0, 200, 300, or 400 mg kg-1 day-1 for 10 months. Methoxychlor treatment delayed puberty by as much as 10 weeks and reduced fertility and copulatory plug formation in a dose-related manner at the initial mating. During mating, M-treated males exhibited shorter latencies to mount and ejaculate versus control males, but the number of intromissions prior to ejaculation was unaffected, indicating that M enhanced the arousal level in the males in an estrogen-dependent manner. Most treated males eventually mated but time-to-pregnancy was lengthened. Very low sperm counts were associated with infertility, while prolonged delays in puberty reduced fecundity. Methoxychlor treatment with 200 to 400 mg kg-1 day-1 failed to mimic the chronic effects of a sustained (8 months) low dose of estradiol-17 beta (3-mm silastic implants) on pituitary or testicular hormone levels. Estradiol administration increased pituitary weight 4-fold, serum levels of luteinizing hormone (LH) were reduced by almost 50%, and serum prolactin was increased 40-fold, while M did not affect any of these measures. These data demonstrate that M affects the CNS, epididymal sperm numbers, and the accessory sex glands and delays mating without significantly affecting the secretion of LH, prolactin, or testosterone. These data indicate that M did not alter pituitary endocrine function in either an estrogenic or antiandrogenic manner. To our knowledge, these data provide the first in vivo example of such a pronounced degree of target tissue selectivity to an environmental endocrine-disrupting chemical"
Keywords:		"Animals Dose-Response Relationship, Drug Insecticides/pharmacology/*toxicity Luteinizing Hormone/drug effects/*metabolism Male Methoxychlor/pharmacology/*toxicity Pituitary Gland/anatomy & histology/drug effects/physiology Prolactin/drug effects/*metaboli;"
Notes:		"MedlineGray, L E Jr Ostby, J Cooper, R L Kelce, W R eng England 1999/04/03 Toxicol Ind Health. 1999 Jan-Mar; 15(1-2):37-47. doi: 10.1177/074823379901500105"