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.
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.
authors: Endocrinology Branch, United States Environmental Protection Agency, Research Triangle Park, NC 27111, USA. gray.earl@epamail.epa.gov
authors: L E
authors: LE
authors: Gray
authors: J
authors: J
authors: Ostby
authors: R L
authors: RL
authors: Cooper
authors: W R
authors: WR
authors: Kelce
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D007306:Insecticides / Q000494:pharmacology / Q000633:toxicity*; D007986:Luteinizing Hormone / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008731:Methoxychlor / Q000494:pharmacology / Q000633:toxicity*; D010902:Pituitary Gland / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D011388:Prolactin / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D013076:Sperm Count / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000502:physiology; D015262:Xenobiotics / Q000494:pharmacology / Q000633:toxicity
chemical_list: D007306:Insecticides; D015262:Xenobiotics; D011388:Prolactin; D007986:Luteinizing Hormone; D008731:Methoxychlor