We have discovered that growth hormones from ternary complexes with their receptors
in which site 1 on the hormone first binds to one molecule of receptor and then
hormone site 2 then binds to another molecule of receptor, thereby producing a
1:2 complex. We believe this phenomenon is shared by other ligands having similar
conformational structure. Assays based on this phenomenon are useful for identifying
ligand agonists and antagonists. Sites 1 and 2 are structurally identified to facilitate
generation of amino acid sequence variants of ternary complex-forming ligands.
Novel variants of growth hormone, prolactin placental lactogen and other related
ligands are provided. As a result of our studies with the ternary complex we have
determined that selected antibodies to the receptor for these ligands are capable
of acting as ligand agonists or antagonists. Novel growth hormones and novel uses
for anti-growth hormone receptor antibodies are described.