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Title: The environmental chemical tributyltin chloride (TBT) shows both estrogenic and adipogenic activities in mice which might depend on the exposure dose

Abstract

Exposure during early development to chemicals with hormonal action may be associated with weight gain during adulthood because of altered body homeostasis. It is known that organotins affect adipose mass when exposure occurs during fetal development, although no knowledge of effects are available for exposures after birth. Here we show that the environmental organotin tributyltin chloride (TBT) exerts adipogenic action when peripubertal and sexually mature mice are exposed to the chemical. The duration and extent of these effects depend on the sex and on the dose of the compound, and the effects are relevant at doses close to the estimated human intake (0.5 {mu}g/kg). At higher doses (50-500 {mu}g/kg), TBT also activated estrogen receptors (ERs) in adipose cells in vitro and in vivo, based on results from acute and longitudinal studies in ERE/luciferase reporter mice. In 3T3-L1 cells (which have no ERs), transiently transfected with the ERE-dependent reporter plus or minus ER{alpha} or ER{beta}, TBT (in a dose range of 1-100 nM) directly targets each ER subtype in a receptor-specific manner through a direct mechanism mediated by ER{alpha} in undifferentiated preadipocytic cells and by ER{beta} in differentiating adipocytes. The ER antagonist ICI-182,780 inhibits this effect. In summary, the results ofmore » this work suggest that TBT is adipogenic at all ages and in both sexes and that it might be an ER activator in fat cells. These findings might help to resolve the apparent paradox of an adipogenic chemical being also an estrogen receptor activator by showing that the two apparently opposite actions are separated by the different doses to which the organism is exposed. - Research Highlights: > The environmental organotin tributyltin chloride shows dose-dependent estrogenic and adipogenic activities in mice. > The duration and extent of these effects depend on the sex and the dose of the compound. > The estrogenic and adipogenic effects of TBT occur at doses closed to the estimated human intake. > TBT activates the estrogen receptors (ER{alpha} and ER{beta}) in 3T3-L1 cells at nM concentrations.« less

Authors:
; ;  [1]; ;  [2];  [3];  [4]
  1. Laboratory of Biotechnology and Department of Laboratory Medicine, Civic Hospital of Brescia (Italy)
  2. Centre of Excellence on Neurodegenerative Diseases, University of Milan (Italy)
  3. Center for Integrative Genomics, University of Lausanne (Switzerland)
  4. Human Pathology, School of Medicine, University of Brescia (Italy)
Publication Date:
OSTI Identifier:
21587815
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 255; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2011.05.017; PII: S0041-008X(11)00208-0; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CHLORIDES; DOSES; ESTROGENS; FAT CELLS; HOMEOSTASIS; IN VITRO; IN VIVO; INTAKE; LUCIFERASE; MICE; ORGANOMETALLIC COMPOUNDS; RECEPTORS; TIN COMPOUNDS; ANIMAL CELLS; ANIMALS; CHLORINE COMPOUNDS; CONNECTIVE TISSUE CELLS; ENZYMES; HALIDES; HALOGEN COMPOUNDS; HORMONES; MAMMALS; MEMBRANE PROTEINS; ORGANIC COMPOUNDS; OXIDASES; OXIDOREDUCTASES; PROTEINS; RODENTS; SOMATIC CELLS; STEROID HORMONES; VERTEBRATES

Citation Formats

Penza, M, Jeremic, M, Marrazzo, E, Maggi, A, Ciana, P, Rando, G, Grigolato, P G, and Di Lorenzo, D., E-mail: dilorenzodiego@yahoo.it. The environmental chemical tributyltin chloride (TBT) shows both estrogenic and adipogenic activities in mice which might depend on the exposure dose. United States: N. p., 2011. Web. doi:10.1016/j.taap.2011.05.017.
Penza, M, Jeremic, M, Marrazzo, E, Maggi, A, Ciana, P, Rando, G, Grigolato, P G, & Di Lorenzo, D., E-mail: dilorenzodiego@yahoo.it. The environmental chemical tributyltin chloride (TBT) shows both estrogenic and adipogenic activities in mice which might depend on the exposure dose. United States. https://doi.org/10.1016/j.taap.2011.05.017
Penza, M, Jeremic, M, Marrazzo, E, Maggi, A, Ciana, P, Rando, G, Grigolato, P G, and Di Lorenzo, D., E-mail: dilorenzodiego@yahoo.it. 2011. "The environmental chemical tributyltin chloride (TBT) shows both estrogenic and adipogenic activities in mice which might depend on the exposure dose". United States. https://doi.org/10.1016/j.taap.2011.05.017.
@article{osti_21587815,
title = {The environmental chemical tributyltin chloride (TBT) shows both estrogenic and adipogenic activities in mice which might depend on the exposure dose},
author = {Penza, M and Jeremic, M and Marrazzo, E and Maggi, A and Ciana, P and Rando, G and Grigolato, P G and Di Lorenzo, D., E-mail: dilorenzodiego@yahoo.it},
abstractNote = {Exposure during early development to chemicals with hormonal action may be associated with weight gain during adulthood because of altered body homeostasis. It is known that organotins affect adipose mass when exposure occurs during fetal development, although no knowledge of effects are available for exposures after birth. Here we show that the environmental organotin tributyltin chloride (TBT) exerts adipogenic action when peripubertal and sexually mature mice are exposed to the chemical. The duration and extent of these effects depend on the sex and on the dose of the compound, and the effects are relevant at doses close to the estimated human intake (0.5 {mu}g/kg). At higher doses (50-500 {mu}g/kg), TBT also activated estrogen receptors (ERs) in adipose cells in vitro and in vivo, based on results from acute and longitudinal studies in ERE/luciferase reporter mice. In 3T3-L1 cells (which have no ERs), transiently transfected with the ERE-dependent reporter plus or minus ER{alpha} or ER{beta}, TBT (in a dose range of 1-100 nM) directly targets each ER subtype in a receptor-specific manner through a direct mechanism mediated by ER{alpha} in undifferentiated preadipocytic cells and by ER{beta} in differentiating adipocytes. The ER antagonist ICI-182,780 inhibits this effect. In summary, the results of this work suggest that TBT is adipogenic at all ages and in both sexes and that it might be an ER activator in fat cells. These findings might help to resolve the apparent paradox of an adipogenic chemical being also an estrogen receptor activator by showing that the two apparently opposite actions are separated by the different doses to which the organism is exposed. - Research Highlights: > The environmental organotin tributyltin chloride shows dose-dependent estrogenic and adipogenic activities in mice. > The duration and extent of these effects depend on the sex and the dose of the compound. > The estrogenic and adipogenic effects of TBT occur at doses closed to the estimated human intake. > TBT activates the estrogen receptors (ER{alpha} and ER{beta}) in 3T3-L1 cells at nM concentrations.},
doi = {10.1016/j.taap.2011.05.017},
url = {https://www.osti.gov/biblio/21587815}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 255,
place = {United States},
year = {Mon Aug 15 00:00:00 EDT 2011},
month = {Mon Aug 15 00:00:00 EDT 2011}
}