Part of “CHAPTER 12 – GROWTH HORMONE AND ITS DISORDERS“

The GHBP is the soluble, extracellular domain of the GHR. In humans and many other species, the GHBP is generated from the GHR by proteolysis; in rodents it is derived from the GHR gene via alternative splicing.13 The GHBP circulates in plasma in nanomolar concentrations, sufficient to complex a substantial part (˜50%) of plasma GH. The serum GHBP level appears to reflect the GHR abundance of the organism, especially in the liver. The biologic significance or importance of the GHBP is not known; it is evolutionarily conserved throughout the vertebrates and is generated by different mechanisms in different species, suggesting an important role. The GHBP modulates GH action through a variety of mechanisms. It inhibits GH
action by competing with the GHR for ligand and by generating “unproductive” heterodimers with the GHR at the cell surface, as opposed to the GHR homodimers necessary for signaling. The GHBP also prolongs the half-life of GH in the circulation by complexing GH, thereby delaying its elimination. The net effect of these modulatory activities in the intact organism is not well understood.