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 (Met14hGH), was able to compete with [125I]hGH for binding to lactogenic receptors in Nb2-11C 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]Met14hGH 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 Met14hGH 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.
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D005260:Female; D013006:Growth Hormone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D019382:Human Growth Hormone; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008223:Lymphoma / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D011981:Receptors, Prolactin / Q000187:drug effects* / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000187:drug effects* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology*
D011981:Receptors, Prolactin; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D013006:Growth Hormone