1: Regul Pept. 2004 Jun 15;119(1-2):113-24. 

Expression of hypothalamic neuropeptides after acute TCDD treatment and
distribution of Ah receptor repressor.

Fetissov SO, Huang P, Zhang Q, Mimura J, Fujii-Kuriyama Y, Rannug A, Hokfelt T,
Ceccatelli S.

Department of Neuroscience B3:4, Karolinska Institutet, Retzius vag. 8, S-171 77
Stockholm, Sweden. Serguei.Fetissov@neuro.ki.se

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant
originating from industrial waste. At sublethal concentrations it induces
anorexia and weight loss as part of the so-called wasting syndrome. To gain
insight into its possible underlying mechanisms, mRNA expression of some key
hypothalamic neuropeptides involved in the regulation of body weight was studied
using in situ hybridization histochemistry in adult male Sprague-Dawley rats 6
days after single oral administration of TCDD (15 microg/kg) and in age-paired
control rats. In TCDD-treated rats which displayed a decrease in body weight
gain vs. controls, arcuate nucleus expression of neuropeptide Y (NPY),
proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript
(CART) mRNA was increased. In the lateral hypothalamic area,
melanin-concentrating hormone (MCH) mRNA expression was also increased, while
levels of CART and orexin/hypocretin mRNA were not significantly changed. Since
TCDD is known to bind to the aryl hydrocarbon receptor (AhR), the distribution
of the AhR repressor (AhRR), which is co-expressed with AhR in the same cells,
was studied by immunohistochemistry in the mouse hypothalamus using mouse AhRR
specific antiserum. AhRR immunoreactivity was present in the nuclei of neurons
found in all main hypothalamic groups including NPY, CART, MCH and
orexin/hypocretin neurons. Xenobiotic response elements were found in these
neuropeptide genes with the exception of MCH. Thus changes in expression of
orexigenic and anorexigenic neuropeptides after TCDD treatment may help to
explain the occurrence of the TCDD-induced weight loss, which may be either
directly or indirectly related to the effects of TCDD on neuropeptide
expression.

PMID: 15093705 [PubMed - indexed for MEDLINE]


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