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Molecular Pharmacology, Vol 15, 515-524, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

Studies on the Estrogenic Activity of Chlordecone (Kepone) in the Rat: Effects on Uterine Estrogen Receptor

WILLIAM H. BULGER 1, ROSEANNA M. MUCCITELLI 1, and DAVID KUPFER 1

1 Worcester Foundation for Experimental Biology, 222 Maple Avenue, Shrewsbury, Massachusetts 01545 U.S.A.

The effects of chlordecone (Kepone) on rat uterine estrogen receptor were examined in vitro and in vivo. In cell free preparations, chlordecone was found to inhibit the binding of [3H]estradiol to uterine cytosolic 8S estrogen receptor in a competitive manner, suggesting that chlordecone binds to the same site as estradiol. Incubation of isolated uteri in vitro in the presence of chlordecone resulted in an increrase in estrogen receptor in the nuclear fraction. This increase accompanied a decline in the amount of estrogen receptor in the cytosolic fraction, indicating that translocation of the estrogen receptor had occurred. Within one hour of the injection of immature rats with chlordecone there was an accumulation of estrogen receptor in the uterine nuclear fraction that was concomitant with a depletion of cytosolic estrogen receptor. The amount of nuclear receptors remained elevated up to 48 hours after chlordecone administration. Cytosolic receptors depletion persisted for 16 hours after injection, at which time replenishment of the cytosolic receptor began. Two hours after chlordecone injection, the ratio of uterine weight to body weight was elevated. Uterine cytosolic protein increased 16-48 hours after injection of chlordecone and the amount of uterine nuclear DNA was elevated 24-48 hours after chlordecone administration. The similarities between the effects of estradiol and chlordecone on uterine estrogen receptors and the effect of the long half life of chlordecone in the animal on the estrogenic action of chlordecone are discussed.

Note:
ACKNOWLEDGMENT The authors gratefully acknowledge the excellent technical assistance of Deborah C. Luper, summer student from the Worcester Polytechnic Institute, Worcester, Massachusetts.

Submitted on August 31, 1978
Accepted on November 6, 1978




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