Document Detail


The reported active metabolite of methoxychlor, 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane, inhibits testosterone formation by cultured Leydig cells from neonatal rats.
MedLine Citation:
PMID:  16199348     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Methoxychlor (MC) is an insecticide that is presently used on agricultural crops, especially after the ban on the use of 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT) in the United States. Following administration in vivo, MC is converted to 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), which is thought to be the active agent. However, both MC and HPTE have been reported to have weak estrogenic and antiandrogenic activities, and they are thought to exert their potential adverse (endocrine disruptive) effects through the estrogen and androgen receptors, respectively. In a recent study, HPTE was shown to inhibit both basal and hCG-stimulated testosterone production by cultured Leydig cells from immature and adult rats, and these effects were reported to be mediated through the estrogen receptor. Because fetal Leydig cells represent a separate population from adult Leydig cells and many of the reported adverse actions of endocrine disruptors are thought to have their effects during gestational exposure, the present studies examined the effects of HPTE on testosterone formation by cultured fetal Leydig cells from neonatal rats to determine whether these cells are sensitive to HPTE. Our studies demonstrated that HPTE inhibited both basal and hCG-stimulated testosterone formation in a dose-dependent manner. Significant declines in testosterone were observed at about 100nM HPTE, and this effect was detected as early as 1h after exposure. The main effects of HPTE appeared to be localized to the cholesterol side-chain cleavage step which converts cholesterol to pregnenolone. In addition, this effect did not appear to be mediated through the estrogen receptor as a weak estrogen or the androgen receptor as an antiandrogen, which are the currently proposed modes of action of MC and HPTE.
Authors:
Eisuke P Murono; Raymond C Derk
Related Documents :
21072308 - Estrogens of multiple classes and their role in mental health disease mechanisms.
18774188 - The healthy cell bias of estrogen action: mitochondrial bioenergetics and neurological ...
18052088 - On the intractability of estrogen-related receptor alpha as a target for activation by ...
15878968 - Transcriptional regulation of dehydroepiandrosterone sulfotransferase (sult2a1) by estr...
11561058 - Unveiling the functions of presynaptic metabotropic glutamate receptors in the central ...
3034918 - Ligand- and weak base-induced redistribution of asialoglycoprotein receptors in hepatom...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Reproductive toxicology (Elmsford, N.Y.)     Volume:  20     ISSN:  0890-6238     ISO Abbreviation:  Reprod. Toxicol.     Publication Date:    2005 Nov-Dec
Date Detail:
Created Date:  2005-10-03     Completed Date:  2006-09-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8803591     Medline TA:  Reprod Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  503-13     Citation Subset:  IM    
Affiliation:
Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Health Effects Laboratory Division, Pathology and Physiology Research Branch, M/S L-2015, 1095 Willowdale Road, Morgantown, WV 26505-2888, USA. eem8@cdc.gov
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
8-Bromo Cyclic Adenosine Monophosphate / pharmacology
Animals
Animals, Newborn
Cells, Cultured
Cholesterol Side-Chain Cleavage Enzyme / antagonists & inhibitors*,  metabolism
Chorionic Gonadotropin / pharmacology
Dose-Response Relationship, Drug
Endocrine Disruptors / toxicity*
Insecticides / metabolism*
Leydig Cells / drug effects*,  metabolism
Male
Methoxychlor / metabolism*
Phenols / toxicity*
Rats
Rats, Sprague-Dawley
Testosterone / metabolism*
Time Factors
Chemical
Reg. No./Substance:
0/Chorionic Gonadotropin; 0/Endocrine Disruptors; 0/Insecticides; 0/Phenols; 23583-48-4/8-Bromo Cyclic Adenosine Monophosphate; 2971-36-0/2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane; 58-22-0/Testosterone; 72-43-5/Methoxychlor; EC 1.14.15.6/Cholesterol Side-Chain Cleavage Enzyme

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


Previous Document:  Cardiovascular emergencies in the pediatric patient.
Next Document:  The use of levomepromazine in Hyperemesis Gravidarum resistant to drug therapy--a case series.