Certain large forms of circulating immunoreactive human growth hormone are in fact immunoglobulins.
To explain frequent discordances between serum GH levels and clinical manifestation of acromegaly, we investigated the possibility that certain immunoglobulins G (IgGs) might be responsible for the displacement of [125I]human (h) GH in the hGH RIA. We incubated dilute sera from seven active acromegalics (basal immunoreactive hGH, 22-313 micrograms/L) with rat adipocyte plasma membranes adsorbed on polystyrene plates. IgGs that bound to GH receptor sites in the absence and presence of 250 nM hGH (for nonspecific binding) were detected using anti-hIgG (Fc-specific) antibody conjugated with alkaline phosphatase. In this system two of the seven sera studied tested positive for IgGs against GH-binding sites (serum 4 in 1:400 dilution, and serum 7 in 1:10 dilution). We studied further the serum with the highest titer. On Sephadex G-100, most of the GH-like immunoreactivity (assayed by RIA) present in serum 4 coeluted with IgGs (assayed by immunodiffusion) as a high mol wt (greater than or equal to 150 kDa) component. To confirm its IgG nature, this material was then adsorbed on protein-A-Sepharose and eluted with 0.1 M sodium citrate, pH 3.0. The protein-A-purified IgGs from serum 4 bound specifically to GH receptor sites in adipocyte membranes and displaced [125I]hGH in the hGH RIA. In contrast, IgGs purified from another acromegalic patient (313 micrograms/L hGH) repeatedly tested negative in the membrane binding assay and hGH RIA.(ABSTRACT TRUNCATED AT 250 WORDS)
Campino
C
C
Laboratorio de Endocrinología, Facultad de Medicina, Santiago, Chile.
Szecowka
J
J
Michelsen
H
H
Serón-Ferré
M
M
D000172:Acromegaly / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D000273:Adipose Tissue / Q000166:cytology; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D005189:False Positive Reactions; D005260:Female; D013006:Growth Hormone / Q000032:analysis* / Q000145:classification; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis* / Q000145:classification / Q000302:isolation & purification; D008297:Male; D010316:Particle Size; D011863:Radioimmunoassay; D011986:Receptors, Somatotropin / Q000032:analysis
D007074:Immunoglobulin G; D011986:Receptors, Somatotropin; D013006:Growth Hormone