1179 MODULATION OF SOMATOMEDIN RECEPTOR SITES IN GROWTH HORMONE-TREATED HYPOPITUITARY DWARFS

Abstract

We have previously demonstrated that somatomedin (SM) can induce the loss of specific SM-C receptors on cultured IM-9 lymphocytes in a time- and concentration-dependent manner. To investigate the acute regulation of SM binding under in vivo conditions, we have evaluated SM receptors on circulating mononuclear cells obtained from 12 hypopituitary dwarfs prior to and after 4 days administration of hGH, 0.1 U/kg/day. Plasma SM levels, measured by radioreceptorassay, rose from 0.37 ± 0.08 U/ml (mean ± SEM) to 1.00 ± 0.10 (p< 0.001). Concomitantly, specific binding of 125-I-SM-C to 50 ×106 mononuclear cells/ml fell from 13.61 ± 0.97% to 10.40 ± 0.85% (p< 0.02). Scatchard analysis demonstrated that the decrease in specific binding was predominantly secondary to a reduced number of SM-C receptor sites per cell, with no alteration in receptor affinity. Overall, a significant inverse correlation was observed between plasma SM levels and mononuclear cell binding of 125-I-SM-C (r=-0.62, p< 0.001).The data demonstrate that treatment of hypopituitarism with conventional therapeutic doses of hGH results in significant acute increases in plasma SM levels in the majority of subjects, with a reciprocal decline in the specific binding of 125-I-SM-C. We conclude that SM, like insulin, is capable of regulating homologous receptor concentrations under both in vitro and in vivo conditions.