Studies with a panel of monoclonal antibodies (MAbs) reactive towards the presumptive rabbit liver growth-hormone (GH) receptor show that the rabbit serum GH-binding proteins share seven antigenic determinants (three at the hormone-binding site and four located elsewhere) with the liver cytosolic GH-binding proteins and the putative GH ‘receptors’ associated with the hepatocyte membrane. The rabbit serum binding proteins have an affinity for GH similar to the membrane GH receptors [for human GH, Ka = 2.45 (+/- 0.15) X 10(9) M-1 (mean +/- S.E.M., n = 8)] and high capacity relative to membrane ‘GH receptors’. Analogues of the postulated membrane ‘receptor’ subtypes 1 and 2 exist in the serum, but not subtype 3, which is also absent from liver cytosol. The serum and cytosolic binding proteins have identical cation-dependence properties; hGH binding is Ca2+-dependent, whereas oGH binding is Ca2+-independent. Affinity labelling of hGH-affinity-purified serum binding proteins with 125I-hGH demonstrated a major GH-binding subunit, of Mr 55,000, identical with the major component purified from membranes. In view of their high affinity and capacity, the serum binding proteins could control availability of GH to membrane receptors. It is suggested that the cytosolic binding proteins may be newly synthesized serum binding proteins. The existence of a close relationship between subsets of membrane-associated GH-binding sites, the serum GH-binding proteins and cytosolic GH-binding proteins dictates a reappraisal of earlier ligand-binding studies, which did not distinguish between binding-site subsets in the liver.

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