In Vivo Exposure of Young Adult Male Rats to Methoxychlor Reduces Serum Testosterone Levels and Ex Vivo Leydig Cell Testosterone Formation and Cholesterol Side-Chain Cleavage Activity

Details

• Personal Author:
  Akgul Y ; Derk RC ; Murono EP
• Description:
  Methoxychlor (MC) was developed as a replacement for the banned pesticide DDT. After in vivo administration, it is metabolized in the liver 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 shown to exhibit weak estrogenic and antiandrogenic activities, and they are thought to exert their effects through estrogen and androgen receptors, respectively. Although in vitro studies using cultured rat Leydig cells have reported that HPTE inhibits both basal and hCG-stimulated testosterone formation, the response of circulating testosterone levels to in vivo MC has been more variable. Therefore, the current studies evaluated whether the daily in vivo administration of MC (0, 5, 40 and 200mg/kg body weight) for a short duration (days 54-60 of age) by gavage altered serum testosterone levels and ex vivo Leydig cell testosterone formation in young adult male rats. These results demonstrate that both fluid-retained and fluid-expressed seminal vesicle weights declined to 44 and 60% of control, respectively, in the 200mg/kg MC-exposed animals. Similarly, serum testosterone and dehydroepiandrosterone levels declined to 41 and 45% of control, respectively, in the 200mg/kg MC-exposed animals; however, serum LH and FSH levels were unaffected. Ex vivo Leydig cell basal testosterone formation over 4h declined to 49% of control in animals exposed to 200mg/kg MC, and ex vivo Leydig cell P450 cholesterol side-chain cleavage activity declined to 79 and 50% of control in animals exposed to 40 and 200mg/kg of MC, respectively, supporting previous in vitro studies which demonstrated the sensitivity of this step to MC. [Description provided by NIOSH]
• Subjects:
  • Animals
  • Endocrine System
  • Environmental Monitoring
  • Insecticides
  • Laboratories
  • Occupational Health
  • Safety
• Keywords:
  • Laboratory-animals
  • Animals
  • Animal-studies
  • In-vivo-studies
  • Exposure-assessment
  • Pesticides
  • Pesticides-and-agricultural-chemicals
  • Hormones
• ISSN:
  0890-6238
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  148-153
• Volume:
  21
• Issue:
  2
• NIOSHTIC Number:
  nn:20029570
• Citation:
  Reprod Toxicol 2006 Feb; 21(2):148-153
• Contact Point Address:
  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
• Email:
  eem8@cdc.gov
• CAS Registry Number:
  • 2,2-Bis(p-hydroxyphenyl)-1,1,1-trichloroethane (CAS RN 2971-36-0)
  • Methoxychlor (CAS RN 72-43-5)
• Federal Fiscal Year:
  2006
• NORA Priority Area:
  Disease and Injury: Fertility and Pregnancy Abnormalities
• Peer Reviewed:
  True
• Source Full Name:
  Reproductive Toxicology
• Download URL:
  https://stacks.cdc.gov/view/cdc/190520/cdc_190520_DS1.pdf
• File Type:
  [PDF - 178.04 KB]
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b88d0234c20ee49bb3267c27978909b7e265b2108f5142076076bd6b0f4f4c84bd5b9ccb80c5287c91ca52cf47dc4015a0f6627d1ccb963c58a62ba015019fd2