Effects of Methoxychlor (M) or Its Active Metabolite, 2,2-BIS(p-Hydroxyphenyl)-1,1, 1-Trichloroethane (HPTE), on Testosterone (T) Formation by Cultured Neonatal (Fetal) Leydig Cells (LC)

Details

• Personal Author:
  Derk RC ; Murono EP
• Description:
  M is a pesticide developed as a replacement for dichlorodiphenyltrichloroethane (DDT). Its active metabolite is thought to be HPTE. Both M and HPTE have been reported to exhibit weak estrogenic or antiandrogenic activities, their proposed mechanism(s) of action. In the present studies, we examined the effects of M or HPTE on T biosynthesis by cultured LC from neonatal rats, which represent fetal LC. Increasing concentrations of M or HPTE (100-1000 nM) caused a progressive decline in both basal and 10 mIU/ml human chorionic gonadotropin (hCG)- or 1 mM 8 Br-cAMP-stimulated T following exposure for 4 or 24 h, although the declines with HPTE were greater. To localize the site(s) of action of HPTE, LC were exposed to HPTE (100-1000 nM) for 24 h (both alone or with hCG), then fresh media containing steroid precursors of T were added to assess their conversion to T over 4 h. The conversion of 0.01 mM pregenolone, progesterone or adnrostenedione to T was unaffected by prior exposure to HPTE; however, the conversion of 22(R) hydroxycholesterol to T progressively decreased, suggesting that among the enzymes involved in converting cholesterol to T, P450 cholesterol side-chain cleavage activity is inhibited by HPTE. The concomitant inclusion of the "pure" estrogen antagonist, ICI 182, 780, did not alter the inhibitive effects of HPTE, suggesting that the effects of HPTE are not mediated through the estrogen receptor (ER) pathway. Furthermore, the antiandrogen through the androgen receptor (AR). These results suggest that the two prevailing proposed modes of action of MC/HPTE in altering male reproductive function (weakly estrogenic through the ER or antiandrogenic through the AR) do not apply with respect to their inhibitive effect of T formation by fetal LC. [Description provided by NIOSH]
• Subjects:
  Animals Energy Metabolism Estrogens Insecticides Laboratories Occupational Health Safety Urogenital System
• Keywords:
  Animal-studies Estrogenic-hormones Exposure-levels Laboratory-animals Metabolites Pesticides Reproductive-system
• ISSN:
  1096-6080
• Publisher:
  Society of Toxicology
• Document Type:
  Text
• Genre:
  Abstract or Summary
• 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
• Volume:
  72
• NIOSHTIC Number:
  nn:20022713
• Citation:
  Toxicologist 2003 Mar; 72(S-1):273
• 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:
  2003
• NORA Priority Area:
  Disease and Injury: Fertility and Pregnancy Abnormalities
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah
• Supplement:
  1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:345b182b3df4944944a98232ae052ab0f8cbecb60da52e05811886a1a6ecca547329aa6a7a81573a199adf5edef86386fd4ee30b892d572b813a28aa50da9f15
• Download URL:
  https://stacks.cdc.gov/view/cdc/199387/cdc_199387_DS1.pdf
• File Type:
  [PDF - 56.79 KB ]