Growth Hormone Physiology

Abstract

Human pituitary-derived growth hormone (GH), also known as somatotropin, is encoded by the GH1 gene, one of the five closely related genes in the 46.8 kb GH1 locus located on chromosome 17q24.2. The five exon-containing GH1 gene generates three transcript variants. The transcript variant 1 (NM_000515.4) encodes the largest of the putative GH isoforms, a protein containing 217 amino acid residues (isoform 1). The removal of the signal peptide (residues 1–26) generates a mature GH polypeptide of 191 residues, corresponding to a molecular mass of 22 kiloDalton (kDa). Although this 22 kDa is the predominant human GH found in the circulation (approximately 90 %), smaller GH isoforms have been described [1]. These include a 20 kDa variant from an alternative in-frame splicing event (NM_022559.3) that lacks 14 amino acid residues in the central coding region (residues 32–46) and a 17 kDa isoform lacking residues 1–66. In this section, we will summarize the known chemistry of the predominant 22 kDa GH isoform (amino acid residue numbering will be based on published nomenclature, which excludes the 26-amino-acid signal peptide). We describe how accumulated biochemical knowledge led to the development of human GH antagonists for GH excess in clinical conditions such as acromegaly as well as to the development of formulations of long-acting recombinant human GH (rhGH) for treatment of GH deficiency.