We investigated whether dehydroepiandrosterone (DHEA) or DHEA-sulfate (S) a¡ected the activities of nuclear receptors, with special reference to constitutive androstane receptor L L (CARL L). Administration of DHEA or DHEA-S enhanced the DNA binding of hepatic nuclear extracts to responsive elements for the retinoic acid receptor, the retinoic acid receptor L L 2 and the peroxisome proliferator activated receptor. The bound complexes were shown to be the CARL L-RXR heterodimer by antibody-supershift assays. The expression of a target gene of CARL L, Cyp2b10, was increased in liver by DHEA or DHEA-S treatment, suggesting that DHEA or DHEA-S actually activated CARL L in vivo. It was suggested that the metabolic conversion of DHEA, DHEA-S to CARL L ligands could occur in vivo and the metabolites could regulate the expression of CARL L target gene expression. Our results provide new insights into the in vivo relationship between DHEA/DHEA-S and CARL L activation.

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To reveal the biological and pathological roles of anti-GM1 antibody in Guillain-Barré syndrome (GBS), we examined its effects on nerve growth factor (NGF) induced TrkA autophosphorylation (NGF-TrkA signaling) in PC12 cells, a sympathetic nerve cell line. The NGF-TrkA signaling is enhanced by exogenous GM1 ganglioside and this phenomenon is regarded as one of the functional aspects of GM1. The IgGs purified from patients' sera inhibited the NGF-TrkA signaling in GM1 pre-incubated PC12 cells. The degrees of inhibition by IgGs from patients paralleled their immunological reactivity to GM1. In addition, the IgGs also inhibited the neurite outgrowth of NGF-treated PC12 cells. Immunoglobulins in the rabbit sera, which were immunized by GM1, also caused a similar suppressive phenomenon. These results suggested that the anti-GM1 antibody could play roles in pathophysiology in anti-GM1 antibody positive GBS through interfering with the neurotrophic action of NGF and GM1 mediated signal modulation including NGF-TrkA signaling. It is suggested that the modulation of GM1 function is one important action of antibodies and could be one of the important mechanisms in GBS.