Modulation of Homologous Receptor Concentratons: A Sensitive Radioassay for Human Growth Hormone in Acromegalic, Newborn, and Stimulated Plasma*

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Abstract
Exposure of cultured lymphocytes (IM-9) to human GH (hGH) leads to a time- and concentration-dependent reduction in binding by the homologous receptor. Decreased binding is due to the loss of specific receptors and can be distinguished from receptor occupancy. We have employed this phenomenon to develop a sensitive and specific receptor modulation assay (RMA) for hGH in unextracted plasma and serum. This radioassay is noncompetitive in nature and is based upon the ability of test samples preincubated with IM-9 cells for 4 h to decrease subsequent binding of [125I]hGH. A reproducible reduction in the binding of [125I]hGH was observed after preincubation of cells with unlabeled hGH at concentrations as low as 1 ng/ml, with a 50‥ reduction at 7 ng/ml. Twenty-eight samples from acromegalic, newborn, and stimulated patients were assayed. The ratio of RIA to RMA for these samples was 0.96 ± 0.03 (mean ± SEM), with a range of 0.69–1.24. There was no evidence of systematic underestimation of hGH values by the RMA, as has been reported for most hGH radioreceptor assays. We conclude that the modulation of homologous receptor concentrations provides a mechanism for sensitive, specific and reliable determinations of hGH levels in unextracted serum and plasma. Since induction of homologous receptor loss presumably requires steps beyond binding to the specific receptor, this assay potentially permits a better measure of biologically active GH.

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