Chimeric bovine-human growth hormone prepared by recombinant DNA technology: Binding properties and biological activity

Lydia Binder, Tikva Vogel, Dan Hadary, Gerard Elberg, Arieh Gertler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

A chimeric bovine GH (amino acids Met-Asp-Gln->1-23) and human GH (hGH) (amino acids 24-191) plasmid was constructed and expressed in Escherichia coii. The purified protein (chimeric GH) exhibited a 2-3 order of magnitude lower affinity toward lactogenic receptors in Nb2 lymphoma cells, microsomal fractions from bovine mammary gland and male rat liver. The affinity towards somatogenic receptors in IM-9 human lymphocytes and male rat liver was decreased to a much lesser degree.This diminished affinity towards lactogenic receptors was accompanied by a parallel decrease in the ability of the chimeric GH to stimulate proliferation of Nb2-11C lymphoma cells and the lipogenesis in bovine mammary gland. This implies that occupation of the respective receptors by either chimeric GH or hGH leads to identical postreceptoral effects. The chimeric GH was also capable of down-regulating the lactogenic receptors in Nb2 lymphoma cells and was recognized by three anti-hGH monoclonal antibodies. These and previously published results indicate that the N-terminal part of hGH is essential for the high affinity binding to lactogenic receptors and subsequent biological effect. Removal or replacement by a corresponding part of bovine GH converts the hormone, respectively to weak antagonist or agonists. Analysis of our data, based on hydropathy index leads us to suggest that the high affinity binding site of the hGH towards lactogenic receptors is mainly confined to amino acids nos. 8-18.

Original languageEnglish
Pages (from-to)923-930
Number of pages8
JournalMolecular Endocrinology
Volume3
Issue number6
DOIs
StatePublished - Jun 1989

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