Possible antiestrogenic activity of lindane in female rats

Abstract

During chronic peroral (PO) treatment of weanling, female Fischer 344 rats with daily injections (0.069 mmol/kg) of either 1,1'-(2,2,2-trichloroethylidene) bis [4-chlorobenzene] (p,p'-DDT), 2,4-dichlorophenoxy acetic acid (2,4-D), or gamma-hexachlorocyclohexane (lindane), the lindane treatment induced a significant 20% increase in body weight after 110 days. Further investigation with 0, 5, 10, 20, and 40 mg/kg lindane confirmed a significant increase in average body weight gain at the two highest doses after ten weeks of treatment. Significantly greater food consumption was observed, and the Lee index indicated that lindane treatment induced obesity. In addition to obesity, lindane caused a delay in vaginal opening, disrupted estrous cycling, reduced pituitary and uterine weight, and elevated food consumption during proestrus (when appetite is normally suppressed by estradiol). These responses suggest that, by inducing alterations in the reproductive function of the female rat and by interfering with hormonal regulation of energy balance, lindane may be antiestrogenic rather than estrogenic as previously proposed.

Combined action of estrogen receptor agonists and antagonists in two-hybrid recombinant yeast in vitro

“…Here, the former two showed similar strong antiestrogenicity with an EC 50 of 4.71 Â 10 À 7 and 4.03 Â 10 À 7 mol/L, respectively, which is consistent with the report that they had similar treatment efficacies in breast cancer (Howell et al, 2004). HCH performed as a weak ER antagonist in the recombinant yeast (EC 50 ¼4.60 Â 10 À 5 mol/L), although both its estrogenic and antiestrogenic activities have been observed in other organisms (Briz et al, 2011;Chadwick et al, 1988;Huang et al, 2006;Raizada et al, 1980). Because the binding of an antiestrogen to ER cannot initiate the expression of the reporter gene lac-Z, the inhibition effect test had to be executed by simultaneously exposing the yeast cells to E2 and the tested antagonist.…”

Polychlorinated biphenyl concentrations in adipose tissue as determinants of abdominal obesity in the elderly

“…Endocrine disrupting compounds are thought to cause obesity by a variety of mechanisms such as altering homeostatic metabolic set points or disrupting appetite controls studies [31][32][33][34] but knowledge of these mechanisms in humans remains limited. One previous study has investigated these associations in the elderly [9], reporting linear relationships for low-chlorinated PCBs (4-5 chlorine atoms) and inverse relationships for highly chlorinated (≥ 7 chlorine atoms) PCBs measured in serum.…”

“…The association between PCBs and obesity, particularly abdominal obesity is supported by several animal studies suggesting that exposure to these compounds alter mechanisms involved in weight homeostasis [31][32][33][34]. However, our knowledge of the effects of environmental chemicals including PCBs on weight gain in humans has not been fully elucidated.…”

Reproductive and Developmental Toxicity of Insecticides

“…Treatment with DDT and chlordecone resulted in persistent estrus in rats. Lindane induced marked disturbances in the estrus cycle, prolonging the proestrus phase considerably and thereby delaying ovulation (Chadwick et al, 1988;Pages et al, 2002, Lahiri et al, 1985.…”