Chronic treatment with tributyltin induces sexually dimorphic alterations in the hypothalamic POMC system of adult mice
Tributyltin (TBT), an antifouling agent found in boat paints, is a common contaminant of marine and freshwater ecosystems. It is rapidly absorbed by organic materials and accumulated in many aquatic animals. Human exposure may depend on ingestion of contaminated food or by indirect exposure from household items containing organotin compounds. TBT is defined as an endocrine disruptor compound (EDC) because it binds to androgen receptors. Moreover, it is also included on the list of metabolic disruptors. The brain is a known target of TBT and this compound interferes with the orexigenic system, inducing a strong decrease in NPY expression in the hypothalamus. In the present experiment, we investigated the effect of a chronic treatment with TBT on the mouse anorexigenic system in both sexes, to look at the pro-opiomelanocortin (POMC) expression in the paraventricular (PVN), dorsomedial (DMN), ventromedial (VMN), and arcuate (ARC) hypothalamic nuclei. The results show a sexually dimorphic effect of TBT on both systems. TBT induced a significant decrease of POMC-positive structures only in female mice in DMN, ARC, and in PVN for both sexes. Apparently, these results show that TBT may interfere with the anorexigenic system in hypothalamic areas involved in the control of food intake, by inhibiting POMC in a sexually dimorphic way. In conclusion, in addition to having a direct effect on fat tissue, the effects of TBT as metabolic disruptor, may be due to gender-specific actions on both orexigenic and anorexigenic hypothalamic systems.
KeywordsEDCs Pro-opiomelanocortin TBT Hypothalamus Sex differences
This study was supported by Ministero dell’Istruzione, dell’Università e della Ricerca–MIUR project “Dipartimenti di Eccellenza 2018–2022” to Dept. of Neuroscience “Rita Levi Montalcini,” University of Torino and Cavalieri-Ottolenghi Foundation, Orbassano, Italy. We are very grateful to Maria Schimenti for her technical help. We would like to thank Alzbeta Talarovicova and Christina Lee, North Carolina State University, Raleigh (NC), USA, for the proofreading of this manuscript.
Compliance with ethical standards
Human and animal rights and informed consent
Animal care and handling was carried out according to the European Union Council Directive of 22th September 2010 (2010/63/UE); the Italian Ministry of Health and the Ethical Committee of the University of Torino approved all the procedures reported in the present study.
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