The Molecular Basis for Growth Hormone–Receptor Interactions

Publisher Summary This chapter discusses the molecular basis for growth hormone (GH)–receptor interactions. A high-resolution mutational and structural analyses of purified components have revealed a great deal about the molecular basis for GH action. The structural and functional aspects of the interactions between hGH and its receptors have been largely elaborated. From these studies, it has been possible to engineer homologs of hGH to bind to the hGH receptor and act as potential antagonists. Receptor-selective and high-affinity analogs have also been constructed based on a combination of alanine scanning and monovalent phage display. From this molecular work, much has been revealed about the biology of hGH. Available data suggests that hGH is stored in the pituitary as a (Zn 2+ .hGH) 2 complex. On release from somatotropic vesicles, it dissociates into a monomeric form and reveals its primary receptor binding site (site 1). Furthermore, the constitutive levels of the hGHbp are considerably below the levels of hGH after pulsatile release. Data indicates that hGH binds to the hGH receptor on cell membranes through site 1 and subsequently forms dimers through site 2. A similar process may occur for hGH to activate the human prolactin receptor, except that Zn 2+ is required for site 1 association. Such receptor dimers are then activated and capable of interacting with other cellular components that may mediate the hGH signal.