Comparative study of in vitro and in vivo modulation of lactogenic and somatotropic receptors by native human growth hormone and its modified analog prepared by recombinant deoxyribonucleic acid technology

A modified analog of human GH (hGH), prepared by recombinant DNA technology, that lacks 13 amino acids at the amino terminus (Met¹⁴ hGH), was able to compete with [¹²⁵I]hGH for binding to lactogenic receptors in Nb2-llC rat lymphoma cells, to somatotropic receptors in IM-9 human lymphocytes, and to both lactogenic and somatotropic receptors in the microsomal fraction of virgin female rat liver. Exposure of intact Nb2 or IM-9 cells to Met¹⁴hGH did not reduce the number of surface or intracellular receptors, as compared to the control without hormone. A parallel exposure to 500-fold lower concentrations of hGH resulted in 77–93% reduction in both surface and intracellular receptors. In contrast to [125I]hGH, [125I]Met uhGH was not taken up by the intact Nb2 lymphoma cells. Infusion of anesthetized female virgin rats for 3 h with hGH down-regulated both lactogenic and somatotropic receptors in the liver. A similar infusion with up to 200-fold higher amounts of MetI4hGH did not lower the number of total receptors, indicating lack of down-regulation. Some decrease in the binding to free receptors was observed, suggesting that Met¹⁴hGH is capable of binding to liver receptors in vivo.