Approximately half of circulating GH is bound to Growth Hormone Binding Protein ((GHBP) Herington et al. 1986), a soluble fragment of the Growth Hormone Receptor (Baumann et al. 1986) formed when the extracellular region is proteolytically cleaved (Leung et al. 1987). This cleavage is mediated by metalloproteases such as TACE (ADAM17, Zhang et al. 2000). The membrane-bound remnant is subsequently degraded by the gamma-secretase complex (Cowan et al. 2005).