Document Detail


The estrogenic and antiandrogenic pesticide methoxychlor alters the reproductive tract and behavior without affecting pituitary size or LH and prolactin secretion in male rats.
MedLine Citation:
PMID:  10188190     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
L E Gray; J Ostby; R L Cooper; W R Kelce
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Toxicology and industrial health     Volume:  15     ISSN:  0748-2337     ISO Abbreviation:  Toxicol Ind Health     Publication Date:    1999 Jan-Mar
Date Detail:
Created Date:  1999-05-25     Completed Date:  1999-05-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8602702     Medline TA:  Toxicol Ind Health     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  37-47     Citation Subset:  IM    
Affiliation:
Endocrinology Branch, United States Environmental Protection Agency, Research Triangle Park, NC 27111, USA. gray.earl@epamail.epa.gov
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MeSH Terms
Descriptor/Qualifier:
Animals
Dose-Response Relationship, Drug
Insecticides / pharmacology,  toxicity*
Luteinizing Hormone / drug effects,  secretion*
Male
Methoxychlor / pharmacology,  toxicity*
Pituitary Gland / anatomy & histology,  drug effects,  physiology
Prolactin / drug effects,  secretion*
Rats
Rats, Inbred Strains
Sexual Behavior, Animal / drug effects*
Sperm Count / drug effects
Testis / drug effects*,  physiology
Xenobiotics / pharmacology,  toxicity
Chemical
Reg. No./Substance:
0/Insecticides; 0/Xenobiotics; 72-43-5/Methoxychlor; 9002-62-4/Prolactin; 9002-67-9/Luteinizing Hormone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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