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ToxSci Advance Access originally published online on September 14, 2005
Toxicological Sciences 2005 88(2):477-484; doi:10.1093/toxsci/kfi322
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Neurobiological Effects of Bisphenol A May Be Mediated by Somatostatin Subtype 3 Receptors in Some Regions of the Developing Rat Brain

Rosa Maria Facciolo*,1, Maria Madeo*, Raffaella Alò*, Marcello Canonaco* and Francesco Dessì-Fulgheri{dagger}

* Comparative Neuroanatomy Laboratory of Ecology Department, University of Calabria, 87030 Arcavacata di Rende-Cosenza, Italy; {dagger} Animal Biology Department, University of Firenze, 50100 Firenze, Italy

Received July 6, 2005; accepted September 8, 2005

Considerable attention has been focused on environmental disruptors such as the xenoestrogen bisphenol A, which influences reproductive, developmental, and cognitive activities through its interaction with specific neuromediating systems in an estrogen-like fashion. In the present study, the effects of this xenoestrogen proved to be preferentially directed toward hypothalamic and extrahypothalamic somatostatin receptor subtype 3, which displayed a higher binding affinity of its specific nonpeptide agonist L-796-778 than that of L-779–976 (subtype 2). One type of action, with respect to animals treated with vehicle alone, consisted of a very strong (p < 0.001) decrease of somatostatin receptor subtype 3 mRNA levels in layer V of the frontoparietal cortex of adult rats (Sprague-Dawley) after transplacental and lactational exposure to bisphenol A (400 µg/kg/day). Similarly, such treatment in 7-day-old rats was responsible for a very strong reduction of the subtype 3 mRNA levels in the hypothalamic periventricular nuclei and a strong (p < 0.01) increase of the subtype 3 mRNA levels in the ventromedial nuclei. Moreover, even greater upregulated and downregulated activities were reported when subtype 3 mRNA levels were determined in the presence of receptor agonists specific for distinct {alpha} GABAA receptor subunits ({alpha}1,5). The predominant effects of bisphenol A on somatostatin receptor subtype 3 mRNA levels occurring in an {alpha} GABAA subunit–dependent manner tend to suggest the early modulatory importance of this environmental disruptor on cross-talking mechanisms that are implicated in the plasticity of neural circuits, with consequential influence on neuroendocrine/sociosexual behaviors.

Key Words: nonpeptide agonists; GABAA receptor; xenoestrogens; cortex; hippocampus; hypothalamus.


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