Our Stolen Futurea book by Theo Colborn, Dianne Dumanoski, and John Peterson Myers
 
 

 

Faqi AS and I Chahoud. 1998. Antiestrogenic Effects of Low Doses of 2,3,7,8-TCDD in Offspring of Female Rats Exposed Throughout Pregnancy and Lactation Bulletin of Environmental Contamination and Toxicology 61(4): 462-469

This study reports several significant antiestrogenic effects of low dose in utero and lactational TCDD exposure on female rat offspring. Sexual maturity was delayed significantly in exposed females and uterine weight was significantly reduced. The number of days spent in estrous was decreased in the experimental group exposed to the lowest and intermediate doses, while the group with highest exposure had no significant change. The dose response curve in estrous length is an inverted u-shaped curve, or non-monotonic dose response curve, reported in many low dose studies.

Faqi and Chahoud also present evidence that most exposure from dam to offspring occurs during lactation. They did this by comparing the weights of fetal vs. weanling livers. TCDD levels in the liver at birth were under the limit of detection (0.08ng/g). In contrast, liver concentrations were significantly elevated at the age of weaning.

 


Klinge, CM, JL Bowers, PC Kulakosky, KK Kumboj and HI Swanson. 1999. The Aryl Hydrocarbon Receptor (AHR/AHR nuclear translocator (ARNT) Heterodimer Interacts with Naturally Occurring Estrogen Response Element Molecular and Cellular Endocrinology 157(1-2): 105-19

TCDD (dioxin) binds to the Ah receptor and not to the estrogen receptor (ER). TCDD nonetheless can cause significant antiestrogenic effects. This study investigates the molecular mechanism that allows this "cross-talk." Klinge et al. report that TCDD does not compete with estrogen at the ER, but the Ah receptor in part inhibits estrogen receptor binding to estrogen response elements, thereby inhibiting estrogen action.


Smeets, JM, TR Rankouhi, KM Nichols, H Kamen, NE Kaminski, JP Giesy and M van der Berg. 1999. In vitro Vitellogenin Production by carp (Cyprinus carpio) hepatocytes as a Screening Method for Determining (anti) Estrogenic Activities by Xenobiotics Toxicology and Applied Pharmacology. May 15: 157(1): 68-76

Vitellogenin is the yolk protein precurser produced in the liver of fish. The presence of estradiol stimulates the production of vitellogenin in both male and female fish, and antiestrogens inhibit production. Smeets et al. used hepatocytes taken from carp livers to develop a screening method for testing antiestrogenicity. They exposed cells to tamoxifen and report reduction in vitellogenin production. Similiarly, they tested TCDD and found it to be 10,000 times more potent than tamoxifen in reducing vitellogenin production.

They also tested bisphenol A for estrogenicity. Vitellogenin production increased in both male and female hepatocytes, with a higher level of production in the male than female, compared to controls.

 

 

 

 

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