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ToxSci Advance Access originally published online on July 27, 2008
Toxicological Sciences 2008 106(1):93-102; doi:10.1093/toxsci/kfn150
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© The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Environmentally Relevant Concentrations of 17{alpha}-Ethinylestradiol (EE2) Interfere With the Growth Hormone (GH)/Insulin-Like Growth Factor (IGF)-I System in Developing Bony Fish

Natallia Shved*, Giorgi Berishvili*, Jean-François Baroiller{dagger}, Helmut Segner{ddagger} and Manfred Reinecke*,1

* Division of Neuroendocrinology, Institute of Anatomy, University of Zürich, Winterthurerstr 190, CH-8057 Zürich, Switzerland {dagger} Centre de Coopération Internationale en Recherche Agronomique pour le Développement-Elevage et Médecine Vétérinaire Tropicale, Unité Propre de Recherché 20, 34398 Montpellier, France {ddagger} Centre for Fish and Wildlife Health, University of Bern, Länggass-Str 122, CH-3001 Bern, Switzerland

1 To whom correspondence should be addressed. Fax: +41 44 635-5702. E-mail: reinecke{at}anatom.uzh.ch.

Received March 27, 2008; accepted July 19, 2008


   Abstract

The aim of this study was to evaluate whether effects of environmental estrogens on fish growth and reproduction may be mediated via modulating the growth hormone (GH)/insulin-like growth factor I (IGF-I) system. To this end, developing male and female monosex populations of tilapia were exposed to 17{alpha}-ethinylestradiol (EE2) at 5 and 25 ng EE2/l water from 10-day postfertilization (DPF) until 100 DPF. Under exposure to both EE2 concentrations, sex ratio shifted toward more females and body length, and weight were significantly reduced in males. The growth-reducing effect was associated with significant changes in hepatic IGF-I expression, both in males and females and with significant alterations of IGF-I mRNA and GH mRNA in the brain. The changes in IGF-I and GH mRNA were accompanied by altered estrogen receptor {alpha} (ER{alpha}) expression in brain and liver. These findings point to an influence of estrogenic exposure on the endocrine GH/IGF-I axis. In addition, the EE2 treatment resulted in significant changes of ER{alpha} and IGF-I expression in ovaries and testis, suggesting that the estrogens interact not only with the endocrine but also with the autocrine/paracrine part of the IGF-I system. Overall, our results provide evidence that EE2 at environmentally relevant concentrations is able to interfere with the GH/IGF-I system in bony fish and that the impairing effects of estrogens reported on fish growth and reproductive functions may rather result from a cross talk between the sex steroid and the IGF-I system than be toxicological.

Key Words: IGF-I; growth hormone; development; liver; brain; ovary; testis; teleost.


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