A recently identified thyroid hormone cell surface receptor on the extracellular domain of integrin αVβ3 leads in human cell lines to activation of the mitogen-activated protein kinase (MAPK) signal transduction cascade. Examples of MAPK-dependent thyroid hormone actions are plasma membrane ion pump stimulation and specific nuclear events. These events include serine phosphorylation of the nuclear thyroid hormone receptor, leading to coactivator protein recruitment and complex tissue responses, such as thyroid hormone-induced angiogenesis or tumor cell growth. The existence of this cell surface receptor means that the activity of administered hormone could be limited through structural modification of the molecule to reproduce or inhibit only those hormone actions initiated at the cell surface. Examples of such modifications are provided.