The receptor binding properties of the 20K variant of human growth hormone explain its discrepant insulin-like and growth promoting activities.
The 20K variant of native (22K) hGH is a full agonist for the growth promoting and lactogenic properties of the hormone in vivo but has been reported to have weak or absent insulin-like properties. To explore if these differences may be explained at the receptor level, we compared the ability of 22K and 20K hGH to inhibit the binding of 125I-22K hGH to receptors in isolated rat adipocytes, a target for the insulin-like effects of the hormone and in IM-9 cultured human lymphocytes, more specific for growth effects. Our data show that while 20K hGH is a potent agonist of native 22K hGH in the IM-9 lymphocyte assay, its potency in the rat adipocyte binding assay is only 3%, even when both cells are incubated together in identical conditions. Thus, the receptors for hGH appear to be different on various target cells, explaining why the 20K variant has different relative biological potencies at different sites of action.
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D013006:Growth Hormone / Q000378:metabolism*; D019382:Human Growth Hormone; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011986:Receptors, Somatotropin
D007328:Insulin; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D011986:Receptors, Somatotropin; C039519:somatotropin 20K; D019382:Human Growth Hormone; D013006:Growth Hormone