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The effects of the reported active metabolite of methoxychlor, 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane, on testosterone formation by cultured Leydig cells from young adult rats.

Authors
Murono-EP; Derk-RC
Source
Reprod Toxicol 2004 Nov; 19(1):135-146
NIOSHTIC No.
20025471
Abstract
Methoxychlor (MC) is an insecticide that is currently used on a variety of agricultural crops, especially following the ban of 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT) use in the United States. Following in vivo administration, MC is converted to 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), which is proposed to be the active agent. Both MC and HPTE have been demonstrated to exhibit weak estrogenic and antiandrogenic activities, and they are thought to exert their effects through estrogen or androgen receptors, respectively. A recent study reported that HPTE inhibited both basal and hCG-stimulated testosterone formation by immature and adult cultured rat Leydig cells and that this effect was mediated through the estrogen receptor. In the current studies, we examined the effects of HPTE on basal and hCG-stimulated testosterone formation by cultured Leydig cells from young adult rats. In addition, we evaluated whether the effects of HPTE on rat Leydig cell testosterone biosynthesis were mediated through the estrogen receptor as an estrogen agonist or the androgen receptor as an antiandrogen. The current studies demonstrated that HPTE inhibited both basal and hCG-stimulated testosterone formation in a dose-dependent manner with significant declines in testosterone being observed at approximately 100nM. The effects of HPTE were localized to the cholesterol side-chain cleavage step; however, these effects were not mediated through the classic estrogen receptor or by its acting as an antiandrogen, the currently recognized modes of action of MC and HPTE.
Keywords
Insecticides; Laboratory-animals; Animals; Animal-studies; Agricultural-industry; Agricultural-chemicals; In-vivo-studies; Pesticides; Pesticides-and-agricultural-chemicals
Contact
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, USA
CODEN
REPTED
CAS No.
2971-36-0; 72-43-5
Publication Date
20041101
Document Type
Journal Article
Email Address
eem8@cdc.gov
Fiscal Year
2005
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
0890-6238
NIOSH Division
HELD
Priority Area
Disease and Injury: Fertility and Pregnancy Abnormalities
Source Name
Reproductive Toxicology
State
WV
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