The primary amino acid sequences of the non apeptides secreted by the posterior pituitary gland are shown in Figure 1. The disulfide bridge between Cys residues 1 and 6 results in a peptide with a cyclic portion consisting of six amino acids and a tail of three aminos. These peptides, which share all except two of their nine amino acids, were the first from the pituitary gland whose sequences were determined.
Fig1. The primary structures of arginine vasopressin (AVP) and oxytocin (OCT). In pigs, the amino acid at position 8 is lysine (LVP).
The broad conservation of the similarities in the structures of the two hormones, as well as mode of their synthesis and secretion and receptor structure, suggest a common ancestral gene for the two peptides. The location and structural organization of the genes for oxytocin and vasopressin, OXT and AVP, are also consistent with the likelihood that they arose from a common ancestral gene. As shown in Figure 2, in humans the two genes appear in tandem on chromo some 20, separated by 8 kilobases, and have nearly identical structure. The three exons of the genes are transcribed and translated into a pre-prohormone consisting of a signal peptide followed by the amino acids of oxytocin or vasopressin, a peptide-specific neurophysin (NPI for oxytocin, NPII for vasopressin) and, in vasopressin, a terminal sequence encoding a co-secreted peptide known as co-peptin. Not surprisingly, the neurophysins also share a great deal of sequence homology.
Fig2. The location and structural organization of the OT and VP genes. A. The genes for vasopressin (VP) and oxytocin (OT; purple) are shown in their head-to-head tandem arrangement on chromosome 20, B. The exon/intron structure (top) and peptide processing of the VP and OT pre-prohormones (middle) are virtually identical. The first exon (yellow) and part of the second (orange) encodes the signal peptide and either OT (bottom, light blue) or VP (bottom, magenta), depending on the gene. The large midportion of the second exon encodes either neurophysin I (OT; bottom, gray) or neurophysin II (VP; bottom, green), both 93–95 amino acids. The terminal portion of the second exon and the third exon of the VP gene encodes the protein copeptin.
