ToxSci Advance Access originally published online on October 12, 2005
Toxicological Sciences 2006 89(1):257-264; doi:10.1093/toxsci/kfj012
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The Endocrine Disruptor Atrazine Accounts for a Dimorphic Somatostatinergic Neuronal Expression Pattern in Mice
* Comparative Neuroanatomy Laboratory, Department of Ecology, University of Calabria, 87036 Cosenza, Italy; Section of Behavioural Neurosciences, Department of Cellular Biology and Neuroscience–Istituto Superiore di Sanità, 00161 Roma, Italy; and Department of Animal Biology, University of Firenze, 50100 Firenze, Italy
Received July 27, 2005; accepted September 29, 2005
It has now been established that a large number of man-made and natural chemicals are capable of interfering with the action of natural hormones. In this category "endocrine disruptors" such as the herbicide atrazine, when administered at ecological low doses (1 or 100 µg/kg per day) from gestational day 14 to postnatal day 21, provided a clear dimorphic neurodegenerative pattern in some brain areas of the domestic mouse (Mus musculus). Indeed, the high concentration (100 µg/kg per day) with respect to the low concentration (1 µg/kg per day) induced relevant neuronal damage in extrahypothalamic sites, such as the cortical and striatal areas in both sexes. Marked alterations in other areas, including the hippocampal and hypothalamic nuclei, were mostly typical of the female. At the neuronal level, the neuropeptide somatostatin, specific for the secretion of growth hormone, seemed to be a major target of atrazine effects, as demonstrated by evident subtype2,3,5 receptor mRNA differences of this neuropeptide, at least for the first two subtypes. In particular, a very strong (p < 0.001) upregulation of subtype2 expressing neurons was detected in female hypothalamic areas, specifically the suprachiasmatic nucleus, whereas a similar downregulatory trend was reported for some extrahypothalamic areas such as the striatum. Interestingly, very strong upregulatory and downregulatory actions were detected for neurons expressing subtype3 in male hypothalamic and amygdalar regions and in the cortical and hippocampal areas, respectively. Overall, it appears that these first neurotoxicological effects of atrazine are very likely linked to dimorphic expression patterns of specific somatostatin subtypes in discrete but key hypothalamic and extrahypothalamic areas of Mus musculus.
Key Words: atrazine; herbicide; dimorphism; somatostatinergic receptor subtypes; mice.