title: Growth-hormone-binding protein in patients with acromegaly.
abstract: The present study was undertaken to investigate the possible regulatory effect of chronic exposure to human growth hormone (hGH), in patients with acromegaly, on growth-hormone-binding protein (GH-BP). Nineteen patients with active acromegaly, before, during or after treatment, comprised the subjects of this study. Serum GH was measured by radioimmunoassay and GH-BP by a binding assay with dextran-coated charcoal separation. The specific binding of [125I]hGH (1 ng) obtained with 50 microliters serum was expressed as a percentage of total cpm. To evaluate the impact of the lower GH-BP on GH activity, we studied the effect of acromegalic serum on hGH displacement of [125I]hGH binding to GH receptors in rabbit liver membranes. Compared to normal controls (11.43 +/- 0.37%), the acromegalic patients had low serum levels of GH-BP (5.45 +/- 0.40%; p < 0.001), which correlated negatively with serum GH levels (p < 0.01). In 7 patients, GH-BP normalized within 2-3 months of successful therapy. The lower GH-BP was due to a reduction in binding capacity, whereas binding affinity remained unchanged. Acromegalic serum, with its low GH-BP, resulted in a shift to the left of the GH displacement curve when compared with normal human sera: IC50 values were 7.47 +/- 0.29 and 11.19 +/- 0.84 ng (p < 0.02) for acromegalic and normal human sera, respectively. We conclude that acromegaly is characterized by low levels of GH-BP due to a decrease in serum-binding capacity. The decrease in GH-BP may render the acromegalic serum GH relatively more active in the GH receptor assay.
authors.affiliation: Department of Pharmacology, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
authors.forename: T
authors.initials: T
authors.lastname: Amit
authors.forename: S
authors.initials: S
authors.lastname: Ish-Shalom
authors.forename: B
authors.initials: B
authors.lastname: Glaser
authors.forename: M B
authors.initials: MB
authors.lastname: Youdim
authors.forename: Z
authors.initials: Z
authors.lastname: Hochberg
mesh_terms: D000172:Acromegaly / Q000097:blood* / Q000628:therapy; D000328:Adult; D000368:Aged; D000818:Animals; D001681:Biological Assay; D002352:Carrier Proteins / Q000097:blood*; D005260:Female; D013006:Growth Hormone / Q000097:blood*; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D011986:Receptors, Somatotropin / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C051815:somatotropin-binding protein