Enhancement of gap junctional communication and connexin43 expression by thyroid hormones

Cells in tissues coordinate their activity by sharing ions, second messengers, and small metabolites through clusters of intercellular channels called gap junctions. The thyroid hormones 3,3',5-triiodo-L-thyronine (T3) and L-thyroxine (T4) are capable of modulating gap junctional communication (GJC) as are 1,25-dihydroxyvitamin D3, retinoic acid, and other nuclear receptor ligands. T3 and T4 were found to stimulate GJC in WB-F344 rat liver epithelial cells dose-dependently at concentrations between 1 nM and 0.1 microM, assayed by the dye transfer method using Lucifer Yellow CH. The stimulation of cell-cell communication was preceded by an increase in connexin43 mRNA levels and was accompanied by an accumulation of connexin43 protein measurable 2 days after incubation with these compounds. These observations establish a novel role of thyroid hormones in the regulation of gap junctional intercellular communication via connexin43 gene expression.