Lindane does not alter the estrogen receptor or the estrogen-dependent induction of progesterone receptors in sexually immature or ovariectomized adult rats.
Lindane, gamma-1,2,3,4,5,6-hexachlorocyclohexane (gamma-HCH), has been shown to disrupt reproductive function in mammals. Many of these adverse effects on female reproduction such as alterations in sexual receptivity, disrupted ovarian cyclicity, reduction in uterine weight and termination of pregnancy are thought to be due to altered ovarian hormone secretions and/or an impaired response to circulating estrogen. It has been suggested that gamma-HCH may block the response of estrogen-dependent tissues to estradiol via an interaction with the estrogen receptor. To test this hypothesis, estrogen (ER) and progesterone (PR) receptor affinity and number were evaluated in sexually immature, 17 beta-estradiol-3-benzoate (EB)-primed Long Evans female rats following exposure to vehicle or gamma-HCH (40 mg/kg) for 7 days (Study 1) and in adult, ovariectomized EB-primed Long-Evans rats following gavage with vehicle or gamma-HCH (0, 10, 20, or 40 mg/kg) for 5 days (Study 2). Chlordecone (kepone; 40 mg/kg; i.p.) was used in Study 2 as a positive control for the alteration of the estrogen-induction of PR in the pituitary. Neither gamma-HCH nor chlordecone altered serum estradiol concentrations. gamma-HCH did not change the ER number (1, 24, or 30 h after EB) or the estrogen-dependent induction of PR (24 or 48 h after EB) in the hypothalamus (HYP), pituitary, or uterus. These data indicate that the effects of gamma-HCH on the female reproductive system do not involve an alteration in the ER and that heterogeneity exists between target tissues in their response to xenobiotics.
Laws
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SC
Reproduction Toxicology Branch, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Carey
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SA
Hart
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Cooper
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RL
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004967:Estrogens / Q000502:physiology*; D005260:Female; D001556:Hexachlorocyclohexane / Q000633:toxicity*; D007031:Hypothalamus / Q000378:metabolism; D010052:Ovariectomy; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects* / Q000378:metabolism; D012741:Sexual Maturation; D014599:Uterus / Q000378:metabolism
D004967:Estrogens; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D001556:Hexachlorocyclohexane