Introduction

Circulating human growth hormone (hGH) is a mixture of different molecular variants, the 22 kDa being the most abundant and the major bioactive molecule (Lewis et al., 1978; Baumann, MaCart & Amburn, 1983; Baumann, 1991). This molecule consists of 191 amino acids encoded by the pituitary-transcribed GH gene localized on chromosome 17. The fully translated protein is arranged in a double helix, containing two binding sites for the GH receptor. Dimerization of the receptors is the first step of signal transduction in the target cells (Cunningham et al., 1991; Ultsch, de Vos & Kossiakoff, 1991; Waters et al., 1994; Gertler et al., 1996). The second most abundant GH molecule is the 20 kDa variant, which differs from the 22kDa molecule in missing amino acids 32–46. Di- and oligomcric GH molecules constitute other circulating forms of GH, which also exist in several fragmental forms, e.g. 5 kDa, 17kDa and acidic forms. In the circulation 22 kDa GH is partially bound to two binding proteins, a high-affinity low-capacity which has been known since 1986 (Leung et al., 1987; Spencer et al., 1988), and a low-affinity high-capacity binding protein, which so far has not been precisely described (Baumann & Shaw, 1990; Kratzsch, Selisko & Birkcnmcier, 1995). The amino acid sequence of the high-affinity GH binding protein (GHBP) has been demonstrated to be identical to that of the extracellular domain of the GH receptor, implying a molecular weight of the high-affinity binding protein of approximately 60 kDa (Leung et al., 1987; Spencer et al., 1988) consisting of a 197 amino acid residue of approximately 28 kDa and a glucose moiety.