Whole body action of xenoestrogens with different chemical structures in estrogen reporter male mice
Introduction
The actual concern on the activity of environmental estrogens regards in part their action as ER modulators in the whole body (Di Lorenzo et al., 2002, Palanza et al., 2001, Nagel et al., 2001, Den Hond et al., 2001, Hoyer, 2001). They may interfere with ER-ligands such as endogenous estrogens, therapeutics and with beneficial estrogens present in food. Recent acquisitions allow to hyphotesize that negative effects on normal endocrine function and on hormone dependent pathologies may be caused by blood concentration of estrogenic chemicals as low as those released from fat depots during diets or diseases (Pelletier et al., 2003).
The availability of reporter mice in which the state of transcriptonal activity of estrogen receptors can be investigated in all the estrogen target organs (ERE-tK-LUC mice) (Ciana et al., 2001), provides an opportunity to measure the tissue specific activity of xenoestrogens at relatively low doses and after mobilization out of fat tissue induced by dietary restriction. Here we demonstrate that three compounds βBHC, p,p′DDT and p,p′-DDE are mobilized differently during weight loss and exert compound-specific effects in ERs expressing tissues of male mice.
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Experimental animals
The procedures involving the animals and their care were conducted in accord to institutional guidelines, which comply with national and international laws and policies [National Institutes of Health, Guide for the Care and Use of Laboratory Animals, 1996 (7th edition) (Washington, D.C.); National Academy Press, National Research Council Guide, htpp://www.nap.edu/readingroom/books/labrats]. ERE-tk-LUC transgenic mice were kept in animal rooms maintained at a temperature of 23 °C, with natural
Time dependent ER activation by βBHC, p,p′DDT and p,p′DDE in mouse organs
A time dependent analysis was determined in several tissues of transgenic ERE-iK-LUC reporter male mice (Ciana et al., 2003) injected i.p. with 5000 μg/kg of βBHC, p,p′DDT and p,p′DDE separately. The response was quantified by assaying the enzymatic activity of the transgenic marker, luciferase. In parallel, mice were also treated with 17β-estradiol (50 μg/kg) as a reference compound.
As reported in Fig. 1, all the compounds showed ability to modulate the ERs, time dependently and in a tissue
Discussion
The organochlorines βBHC, p,p′DDT and its main metabolite p,p′DDE, have in common a low toxicity, the ability to concentrate in the food chain and to be extremely long-lived in the adipose tissues of animals and humans (Jaga and Dharmani, 2003).
Previous reports have shown a variable mobilization capacity of environmental chemicals (Diel et al., 2000) from sites of accumulation and a consequential different biological action in the uterus (Bigsby et al., 1997). Here we have shown, that the blood
Acknowledgments
We are grateful to Francesca Piazza, Alessandro Bulla and Rosa Di Lorenzo for their helpful English writing and secretarial assistance. This work was partially supported by the European Union “EDERA”, grant no. QLK4-CT-2002-02221, by Istituto Superiore di Sanità (ARACNA Project) and by the FIRB grant n.er RBNE0157EH.
References (22)
- et al.
Ability of xeno- and phytoestrogens to modulate expression of estrogen-sensitive genes in rat uterus: estrogenicity profiles and uterotrophic activity
J. Steroid Biochem. Mol. Biol.
(2000) - et al.
Histopathological and biochemical changes in guinea pigs after repeated dermal exposure to benzene hexachloride
Toxicology
(1978) - et al.
Lindane-induced macrophage activating factor (MAF) production by peripheral blood leukocytes (PBLs) of rainbow trout (Oncorhynchus mykiss): involvement of intracellular cAMP mobilization
Aquat. Toxicol.
(2002) Reproductive toxicology:current and future directions
Biochem. Pharmacol.
(2001)- et al.
Effects of prenatal exposure to low doses of diethylstilbestrol, o,p′DDT and methoxychlor on postnatal growth and neurobehavioural development in male and female mice
Horm. Behav.
(2001) - et al.
Xenobiotics released from fat during fasting produce estrogenic effects in ovariectomized mice
Cancer Res.
(1997) A rapid and sensitive method for the quantification of microgram quantities of proteins utilizing the principle of protein-dye bining
Anal. Biochem.
(1976)- et al.
Engineering of a mouse for the in vivo profiling of estrogen receptor activity
Mol. Endocrinol.
(2001) - et al.
In vivo imaging of transcriptionally active estrogen receptors
Nat. Med.
(2003) - et al.
BHC induced testicular impairments in rats
Ind. J. Physiol. Pharmacol.
(1990)
Sexual maturation in relation to poly chlorinated aromatic hydrocarbons: Sharpe and Skakkebaek’s hypothesis revisited
Environ. Health Perspect.
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