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Molecular Defects in the Growth Hormone Receptor

Using a classical molecular'genetics approach, Leung eta/. isolated a rabbit full-length eDNA corresponding to a putative GH receptor mRNA (1). The cloning of this eDNA was based on isolation of a protein by its ability to bind GH, followed by screening of a rabbit liver eDNA library using a synthetic oligonucleotide probe, the sequence of which was derived from one of the tryptic fragment sequences of the protein. A putative human GH receptor eDNA clone has been isolated from a human liver eDNA library screened with a rabbit eDNA probe fragment. These cDNAs encode proteins containing a single membr~ne-spanning domain; they share sequence identity with prolactin receptors isolated from a variety of species (2-5), and have certain homologies with a new cytokine receptor family (6). Human genomic analysis revealed at least ten exons that span 87 kb on chromosome 5 (7). GH has multiple biological effects. however (8, 9), and so this cloning strategy could lead to the isolation of GH receptors involved in different actions of GH. The biological properties of the protein isolated by Leung eta/. remains to be demonstrated.