Heterogeneity of circulating growth hormone

Human growth hormone (GH) represents a family of related proteins arising from two genes, alternative mRNA splicing, and several post-translational modifications. In addition, post-secretory events occur when GH enters the circulation. The full scale of GH heterogeneity is only beginning to be appreciated, and new GH forms or related proteins may be discovered in the future. GH measurements are affected by GH heterogeneity. Immunoassays are influenced by the mixture of GH variants, but are not sensitive to GH binding proteins (GHBPs). In contrast, radioreceptor assays are sensitive to both GH variant mixtures and to the high affinity GHBP. It is hoped that in the future, these problems can be minimized by rigorous characterization of existing antibodies with respect to epitope recognition on various GH forms, and ultimately, by production of GH variant-specific antibodies that permit direct and individual assessment of the circulating members of the GH family.