Growth hormone binding to a circulating receptor fragment--the concept of receptor shedding and receptor splicing.
Recent advances in the understanding of circulating growth hormone binding proteins (GHBP) are reviewed. The high affinity GHBP represents the ectodomain of the GH receptor (GHR); it is either cleaved from membrane-bound GHRs (man, rabbit) or derived from an alternatively spliced GHR mRNA (rodents). Another circulating GHBP, of low affinity and not GHR-related, is only partially characterized. The GHBPs complex about half of the GH in human plasma. They act as a buffer regulating free and bound GH, prolong GH half-life, and modulate GH bioactivity through competition with GHRs for ligand. The plasma levels of both GHBPs are developmentally upregulated during childhood and remain relatively constant thereafter. Different species vary in their regulation of GHBP, with sexual dimorphism and large pregnancy-related changes in some but not all species. A variety of conditions associated with altered GH responsivity (resistance or hypersensitivity) are attended by altered levels of the high affinity GHBP. Generally, GH resistance is characterized by decreased GHBP levels, and the converse is true in GH hypersensitivity such as in obesity. It has been postulated that the plasma GHBP level reflects tissue concentrations of the GHR, but this remains to be proven. The high affinity GHBP appears to be positively, though imperfectly, linked to GH action. Soluble receptor isoforms analogous to the GHBP have been demonstrated for several members of the cytokine receptor family to which the GHR belongs. The ultimate biological role of these circulating receptor ectodomains remains to be fully defined.
Baumann
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Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA.
D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000097:blood*; D002648:Child; D004194:Disease; D005260:Female; D005333:Fetus; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D007223:Infant; D010446:Peptide Fragments / Q000097:blood; D011247:Pregnancy; D011817:Rabbits; D011986:Receptors, Somatotropin / Q000378:metabolism*; D012016:Reference Values
D015415:Biomarkers; D002352:Carrier Proteins; D010446:Peptide Fragments; D011986:Receptors, Somatotropin; D013006:Growth Hormone; C051815:somatotropin-binding protein