(A) Multiple forms of thyroid hormone receptors (TRs). Amino acid numbers refer to those in the rat proteins. Adapted with permission from Lazar (8). (B) Data from Lazar et al. (11) demonstrating that TRα2 does not bind thyroid hormone. Rat TRα2 (r-erbAα-2) produced in rabbit reticulocyte lysate does not bind thyroid hormone (T3). Positive controls for TRα1 (r-erbAα-1) and human TRβ (hc-erbA β) with robust T3 binding are shown. Data reproduced with permission from Lazar et al. (11) and relabeled for nomenclature consistency. (C) Tug-of-war between thyroid hormone–binding, transcriptionally active TRα1 and inactive TRα2 competing for binding sites in target genes. cpm, counts per minute.