SERUM GROWTH-HORMONE BINDING-PROTEIN AND HEPATIC GH BINDING-SITES IN THE LEWIS DWARF RAT - EFFECTS OF IGF-I AND GH

A radioimmunoassay (RIA) for the rat growth hormone binding protein (G HBP) was developed using a synthetic peptide (corresponding to the hyd rophilic carboxyl-terminal sequence of mouse GHBP) as standard and a m onoclonal antibody (MAb 4.3) reactive with this peptide as the primary antibody. The values for GHBP concentration obtained for normal rats using this assay compare favourably with those obtained by gel filtrat ion and ELISA methods. The concentration of GHBP in normal male rats a t 11 weeks of age (680+/-30 ng/ml, SEM, n=9) was significantly less th an the concentration in normal females (943+/-47 ng/ml, SEM, n=25). In 11-week-old dwarf male rats the concentration of GHBP was 423+/-35 ng /ml (n=8); less than in dwarf females (542+/-32, P<0.05, n=9) and norm al males (680+/-30, P<0.001, n=9). The GHBP concentration in dwarf rat s was not age-dependent, whereas in normal females the concentration o f GHBP increased with age. The availability of an RIA which is not sus ceptible to interference by endogenous GH, will facilitate further stu dies on hormonal and nutritional regulation of the rat GHBP. The assay was applied to studying the effects of IGF-I infusion (240 mu g/day f or 1 week) and GH injection (65 mu g/100 g body weight, twice daily fo r 1 week and 4 weeks) on the serum concentration of GHBP in 11-week-ol d Lewis dwarf rats. Hepatic GH binding sites were also measured in des aturated membranes from the same animals. The regulation of GHBP and h epatic GH binding in response to twice-daily GH injection was noncoord inate (after 4 weeks, significant upregulation of the liver GHP, but n o effect on serum GHBP; after 1 week, no effect on either GHR or GHBP) . These effects obtained with injected GH contrast with those reported for continuous GH infusion (upregulation of both GHBP and hepatic GH binding sites after 1 week). Infusion of IGF-I was without effect on s erum GHBP or hepatic GH binding sites. Our results highlight the criti cal role of the pattern and duration of growth hormone administration in the regulation of the serum GHBP and show that elevation of IGF-I i s not responsible for the upregulatory effects previously observed wit h continous GH infusion for 1 week. The ratio of GHBP concentration to body mass did not differ significantly between normal and dwarf rats of the same sex and age, despite significant differences in body mass and in the absolute concentration of GHBP. This suggests a fundamental relationship between body mass and serum GHBP levels.