We have discovered that growth hormones form 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. Methods for inhibiting the growth of
breast cancer cells are also described.