Heterogeneity of growth-hormone receptors detected with monoclonal antibodies to human growth hormone.
The specificity of hormone-receptor interactions has been examined with the aid of monoclonal antibodies (MABs) (EB1, EB2, QA68 and NA71) defining four non-overlapping antigenic determinants on human growth hormone (hGH). The results indicate that growth-hormone receptors in liver obtained from different sources differ with regard to their affinities and relative numbers; they may also differ with respect to the region of the growth-hormone molecule to which they bind. Antibody NA71 effectively inhibited hormone binding to all receptor preparations tested, although with various degrees of potency. Monoclonal antibody EB1 demonstrated a graded inhibition with respect to its ability to block 125I-hGH binding to receptors from various sources, the maximum inhibition being seen in receptor preparations from mouse and ovine liver and the minimum in rat liver. MABs EB2 and QA68 also showed various abilities to inhibit hormone-receptor interaction, depending on the origin of the receptor preparation. Furthermore, the receptor-binding characteristics of hormone-antibody complexes were dependent on whether the binding-site preparation was derived from pregnant, lactating or 'normal' animals. A particularly striking difference between the ability of hormone-MAB complexes to bind to receptors from different sources was seen for microsomes (microsomal fractions) derived from livers of animals of the 'Little' mouse strain. These animals become progressively obese, and it was shown that MABs were considerably more effective in inhibiting 125I-labelled hGH binding to microsomes from phenotypically obese mice than to those derived from their non-obese littermates. The results can be explained by the presence of multiple receptor types for GH, the relative proportions of which vary according to the physiological state of the animal, and possibly between species.
D000818:Animals; D000911:Antibodies, Monoclonal; D000939:Epitopes / Q000032:analysis; D005260:Female; D013006:Growth Hormone / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007774:Lactation / Q000378:metabolism; D051379:Mice; D008862:Microsomes, Liver / Q000276:immunology / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D011247:Pregnancy; D011388:Prolactin / Q000276:immunology; D011817:Rabbits; D051381:Rats; D011986:Receptors, Somatotropin / Q000276:immunology / Q000378:metabolism*; D012756:Sheep; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D000939:Epitopes; D011986:Receptors, Somatotropin; D011388:Prolactin; D013006:Growth Hormone