Species Differences in the Regulation of Type 2 Deiodinase Expression in the Brain by Bacterial Endotoxin

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 414-436-HPT Axis Biology & Action
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-427
Gabor Wittmann*1, John W Harney2, P Reed Larsen2 and Ronald M Lechan1
1Tufts Medical Center, Boston, MA, 2Brigham and Women's Hospital, Boston, MA
Recently, we demonstrated that the administration of bacterial lipopolysaccharide (LPS) to rats induces robust, de novo transcription of the type 2 deiodinase (D2) gene and a 50-100-fold increase in D2 enzymatic activity in the leptomeninges and choroid plexus, which normally do not express D2 (Wittmann et al., 2010 Endocrine Society Meeting, San Diego).  The increase in D2 activity was largely attributed to leptomeningeal and choroid plexus fibroblasts, and meningeal fibroblast-like cells in numerous blood vessels in the brain rather than to expression in infiltrating mononuclear cells.  To determine whether endotoxin has a similar effect on leptomeningeal D2 activation in other animal species, both mice (BALB/c and C57BL/6) and Syrian hamsters were studied.  In both mouse strains, LPS administration did not induce the expression of D2 mRNA in the leptomeninges/choroid plexus and blood vessels as shown by in situ hybridization, but markedly upregulated D2 expression in D2-expressing astrocytes in the cerebral cortex, a response which was barely detectable in the rat.  By enzymatic assay, however, LPS treatment did cause a minor increase in D2 enzymatic activity in the leptomeninges in mice.  The highest increase in D2 activity levels, however, occurred in the cortex, confirming the observation from the in situ hybridization studies.  LPS treatment of Syrian hamsters increased D2 enzymatic activity approximately 60-fold in the leptomeninges and 20-fold in the choroid plexus, a reaction similar to the rat. These data demonstrate substantial differences in the tissue-specific activation of the D2 enzyme among rodent species, and underscore the importance of selecting the animal model that is the most relevant to human pathophysiology.

Nothing to Disclose: GW, JWH, PRL, RML

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: NIH grant DK-37021 and a grant from the Dr. Gerald J. and Dorothy R. Friedman New York Foundation for Medical Research