Diversity and unity in the nuclear hormone receptors: a terpenoid receptor superfamily

The remarkable structural unity among the different members of the nuclear hormone receptor superfamily stands in striking contrast to the diversity of the chemical structures of their ligands. Of the three currently known classes of ligands, steroids, retinoids, and thyroid hormones, the first two share a common biosynthetic pathway. Both are terpenes, which are derived by assembly of isoprene units. This biosynthetic link suggests that the receptors for three other classes of terpenoid hormones, the insect juvenile hormones and the plant hormones gibberellic acid and abscissic acid, may also be members of the superfamily. A number of putative nuclear hormone receptors that do not have known ligands have been isolated. At least some of the ligands for these orphan members of the receptor superfamily may be found on the list of biologically active terpenes. Finally, the terpenoid connection raises interesting issues for the evolution of the receptor superfamily.