Effect of halogenated hydrocarbon insecticides on the metabolism and uterotropic action of estrogens in rats and mice

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Abstract

Treatment of immature female rats with chlordane, dieldrin, heptachlor, lindane, p,p′-DDD, p,p′-DDE, or toxaphene for 7 days stimulated the metabolism of estrone by liver microsomal enzymes and inhibited the increase in uterine wet weight caused by estrone. The daily administration of as little as 2–5 mg/kg of chlordane ip for 7 days reduced the uterotropic action of tritiated estrone and decreased the concentration of tritiated estrogen in the uterus. The total body metabolism of tritiated estrone was enhanced in rats pretreated with 10 or 50 mg/kg of chlordane daily for 7 days. Treatment of adult ovariectomized mice with 25 mg/kg of chlordane once a week for 3 wk increased the metabolism of estradiol-17β by liver microsomal enzymes, reduced the estradiol-17β- or estrone-induced increases in uterine wet weight and decreased the amount of tritiated estrogen found in the uterus after injection of tritiated estradiol-17β or estrone. The administration of 25 mg/kg of p,p′-DDD to mice once a week for 3 wk failed to increase the metabolism of estradiol-17β by liver microsomal enzymes and did not affect the increase in uterine wet weight caused by estradiol-17β or estrone. A decrease in reproductive success was observed when female mice were treated with 25 mg/kg of chlordane once a week for 3 wk.

References (33)

  • R.R. Bernard et al.

    Some effects of DDT on reproduction in mice

    J. Mammal

    (1964)
  • J. Bitman et al.

    Estrogenic action of o,p′-DDT in the mammalian uterus and avian oviduct

    Science

    (1968)
  • D.R. Buhler

    Hepatic drug metabolism in fishes

  • A.H. Conney

    Pharmacological implications of microsomal enzyme induction

    Pharmacol. Rev

    (1967)
  • A.H. Conney et al.

    Decreased central depressant effect of progesterone and other steroids in rats pretreated with drugs and insecticides

    J. Pharmacol. Exp. Ther

    (1966)
  • A.H. Conney et al.

    Effect of pesticides on drug and steroid metabolism

    Clin. Pharmacol. Ther

    (1967)
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    Supported in part by Research Contract PH 43-65-1066 from the Pharmacology-Toxicology Programs, National Institute of General Medical Sciences, National Institutes of Health.

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    Present address: Department of Biochemistry, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.

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