Growth hormone heterogeneity in human pituitary and plasma

Several isoforms of growth hormone (GH) have been identified in humans. There are many reasons for this heterogeneity. At the genetic level, two genes encode GH: GH-N, expressed in the pituitary, and GH-V, expressed in the placenta. At the mRNA level, GH-N undergoes alternative splicing into 20K and 22K isoforms. Post-translationally, 22K GH undergoes modifications, such as acetylation at its amino terminus, deamidation, and oligomerization. The picture is complicated further in the circulation, where GH binds to two GH-binding proteins, each with different affinities for the GH isoforms. In addition, a highly heterogeneous mixture of GH fragments has been demonstrated. The implications of this heterogeneity relate to differences between GH immunoassays, such that assay results cannot be compared between laboratories. The reasons for GH heterogeneity and its practical and clinical implications are considered here.