THE TURNOVER OF GROWTH-HORMONE (GH)-BINDING PROTEIN AND GH RECEPTOR IN RABBIT AND RAT

The present study was undertaken to further explore the comparative dy namics of growth hormone-binding protein (GH-BP) in relation to the tu rnover of the GH-receptor (GH-R) in vivo in rabbits and rats. The stra tegy used was to examine the time course of hepatic GH-R turnover over a 3 h period after cycloheximide treatment, with simultaneous measure ments of serum GH-BP level. In the rabbit we sampled multiple liver bi opsies and serum samples consecutively from each animal. In the rat, e xperiments on individual animals were conducted for each time point. I n the rat, both liver GH-R and serum GH-BP declined after cycloheximid e injection following first-order kinetics. The t1/2 values for GH-R a nd GH-BP were 29.7-44.5 and 82.7-119.5 min (95% confidence limits), re spectively. A significant positive correlation was found between rat l iver GH-R and serum GH-BP (r = 0.85; p < 0.001). In contrast, the decl ine in rabbit liver GH-R, following cycloheximide treatment, was accom panied by simultaneous time-dependent accumulation of serum GH-BP. The t1/2 for rabbit serum GH-BP accumulation was 30.4-67.6 min. Scatchard analysis of [I-125]hGH binding to rabbit GH-BP indicated that the bin ding capacity increased from 2818 +/- 538 fmol/ml, at time zero, to 52 36 +/- 419 fmol/ml following 60 min cycloheximide treatment (p < 0.05) . No significant changes in affinity were observed. Pooling all rabbit data points after cycloheximide injection, a significant negative cor relation was found between liver GH-R and serum GH-BP (r = - 0.58; p < 0.001). Thus, parallel disappearance of hepatic GH-R and serum GH-BP in the rat following cycloheximide treatment contrasts that in the rab bit, in which the decline in hepatic GH-R was accompanied by simultane ous time-dependent accumulation of serum GH-BP.