Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1979 Dec;76(12):6641–6645. doi: 10.1073/pnas.76.12.6641

Estrogenic activity of the insecticide chlordecone (Kepone) and interaction with uterine estrogen receptors.

B Hammond, B S Katzenellenbogen, N Krauthammer, J McConnell
PMCID: PMC411923  PMID: 93289

Abstract

The chlorinated insecticide chlordecone (Kepone) interacts with the estrogen receptor system in the rat uterus in vitro and in vivo. It competes with estradiol for binding to the cytoplasmic receptor in vitro and also induces nuclear accumulation of estrogen receptor sites in uteri in vitro. When injected into immature rats, chlordecone translocates estrogen receptor sites to the uterine nucleus, increases uterine weight, and stimulates the synthesis of the progesterone receptor, an estrogen receptor-mediated process. Its slow onset of action but prolonged duration of interaction with estrogen receptor and stimulation of uterine weight gain and progesterone receptor synthesis indicates that, although it has an affinity for receptor only 0.01-0.04% that of estradiol, its considerable estrogenic activity may likely be derived from its long half-life and bioaccumulative character.

Full text

PDF
6641

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson J., Clark J. H., Peck E. J., Jr Oestrogen and nuclear binding sites. Determination of specific sites by ( 3 H)oestradiol exchange. Biochem J. 1972 Feb;126(3):561–567. doi: 10.1042/bj1260561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bitman J., Cecil H. C., Harris S. J., Fries G. F. Estrogenic activity of o,p'-DDT in the mammalian uterus and avian oviduct. Science. 1968 Oct 18;162(3851):371–372. doi: 10.1126/science.162.3851.371. [DOI] [PubMed] [Google Scholar]
  3. Bulger W. H., Muccitelli R. M., Kupfer D. Studies on the estrogenic activity of chlordecone (Kepone) in the rat: effects on uterine estrogen receptor. Mol Pharmacol. 1979 May;15(3):515–524. [PubMed] [Google Scholar]
  4. Cohn W. J., Boylan J. J., Blanke R. V., Fariss M. W., Howell J. R., Guzelian P. S. Treatment of chlordecone (Kepone) toxicity with cholestyramine. Results of a controlled clinical trial. N Engl J Med. 1978 Feb 2;298(5):243–248. doi: 10.1056/NEJM197802022980504. [DOI] [PubMed] [Google Scholar]
  5. Egle J. L., Fernandez J. B., Guzelian P. S., Borzelleca J. F. Distribution and excretion of chlordecone (Kepone) in the rat. Drug Metab Dispos. 1978 Jan-Feb;6(1):91–95. [PubMed] [Google Scholar]
  6. Eroschenko V. P. Alterations in the testes of the Japanese quail during and after the ingestion of the insecticide kepone. Toxicol Appl Pharmacol. 1978 Mar;43(3):535–545. doi: 10.1016/s0041-008x(78)80013-1. [DOI] [PubMed] [Google Scholar]
  7. Huber J. J. Some physiological effects of the insecticide Kepone in the laboratory mouse. Toxicol Appl Pharmacol. 1965 Jul;7(4):516–524. doi: 10.1016/0041-008x(65)90036-0. [DOI] [PubMed] [Google Scholar]
  8. Jensen E. V., DeSombre E. R. Mechanism of action of the female sex hormones. Annu Rev Biochem. 1972;41:203–230. doi: 10.1146/annurev.bi.41.070172.001223. [DOI] [PubMed] [Google Scholar]
  9. Katzenellenbogen B. S., Gorski J. Estrogen action in vitro. Induction of the synthesis of a specific uterine protein. J Biol Chem. 1972 Feb 25;247(4):1299–1305. [PubMed] [Google Scholar]
  10. Katzenellenbogen B. S., Iwamoto H. S., Heiman D. F., Lan N. C., Katzenellenbogen J. A. Stilbestrols and stilbestrol derivatives: estrogenic potency and temporal relationships between estrogen receptor binding and uterine growth. Mol Cell Endocrinol. 1978 Feb-Mar;10(1):103–113. doi: 10.1016/0303-7207(78)90063-1. [DOI] [PubMed] [Google Scholar]
  11. Katzenellenbogen B. S., Katzenellenbogen J. A. Antiestrogens: studies using an in vitro estrogen-responsive uterine system. Biochem Biophys Res Commun. 1973 Feb 20;50(4):1152–1159. doi: 10.1016/0006-291x(73)91526-x. [DOI] [PubMed] [Google Scholar]
  12. Katzenellenbogen B. S. Synthesis and inducibility of the Uterine estrogen-induced protein, IP, during the rat estrous cycle: clues to uterine estrogen sensitivity. Endocrinology. 1975 Feb;96(2):289–297. doi: 10.1210/endo-96-2-289. [DOI] [PubMed] [Google Scholar]
  13. Katzenellenbogen J. A., Johnson H. J., Jr, Carlson K. E. Studies on the uterine, cytoplasmic estrogen binding protein. Thermal stability and ligand dissociation rate. An assay of empty and filled sites by exchange. Biochemistry. 1973 Oct 9;12(21):4092–4099. doi: 10.1021/bi00745a011. [DOI] [PubMed] [Google Scholar]
  14. Kupfer D. Effects of pesticides and related compounds on steroid metabolism and function. CRC Crit Rev Toxicol. 1975 Oct;4(1):83–124. doi: 10.1080/10408447509163835. [DOI] [PubMed] [Google Scholar]
  15. McBlain W. A., Lewin V. Differing estrogenic activities for the enantiomers of o, p'-DDT in immature female rats. Can J Physiol Pharmacol. 1976 Aug;54(4):629–632. doi: 10.1139/y76-088. [DOI] [PubMed] [Google Scholar]
  16. McFarland L. Z., Lacy P. B. Physiologic and endocrinologic effects of the insecticide kepone in the Japanese quail. Toxicol Appl Pharmacol. 1969 Sep;15(2):441–450. doi: 10.1016/0041-008x(69)90042-8. [DOI] [PubMed] [Google Scholar]
  17. Nelson J. A. Effects of dichlorodiphenyltrichloroethane (DDT) analogs and polychlorinated biphenyl (PCB) mixtures on 17beta-(3H)estradiol binding to rat uterine receptor. Biochem Pharmacol. 1974 Jan 15;23(2):447–451. doi: 10.1016/0006-2952(74)90436-5. [DOI] [PubMed] [Google Scholar]
  18. Palmiter R. D., Mulvihill E. R. Estrogenic activity of the insecticide kepone on the chicken oviduct. Science. 1978 Jul 28;201(4353):356–358. doi: 10.1126/science.78523. [DOI] [PubMed] [Google Scholar]
  19. Philibert D., Raynaud J. P. Progesterone binding in the immature mouse and rat uterus. Steroids. 1973 Jul;22(1):89–98. doi: 10.1016/0039-128x(73)90073-1. [DOI] [PubMed] [Google Scholar]
  20. Schmidt W. N., Sadler M. A., Katzenellenbogen B. S. Androgen-uterine interaction: nuclear translocation of the estrogen receptor and induction of the synthesis of the uterine-induced protein (IP) by high concentrations of androgens in vitro but not in vivo. Endocrinology. 1976 Mar;98(3):702–716. doi: 10.1210/endo-98-3-702. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES