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 dynamics of growth hormone-binding protein (GH-BP) in relation to the turnover of the GH-receptor (GH-R) in vivo in rabbits and rats. The strategy used was to examine the time course of hepatic GH-R turnover over a 3 h period after cycloheximide treatment, with simultaneous measurements of serum GH-BP level. In the rabbit we sampled multiple liver biopsies and serum samples consecutively from each animal. In the rat, experiments on individual animals were conducted for each time point. In the rat, both liver GH-R and serum GH-BP declined after cycloheximide injection following first-order kinetics. The t1/2 values for GH-R and GH-BP were 29.7-44.5 and 82.7-119.5 min (95% confidence limits), respectively. A significant positive correlation was found between rat liver GH-R and serum GH-BP (r = 0.85; p < 0.001). In contrast, the decline in rabbit liver GH-R, following cycloheximide treatment, was accompanied 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 binding capacity increased from 2818 +/- 538 fmol/ml, at time zero, to 5236 +/- 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 correlation 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 rabbit, in which the decline in hepatic GH-R was accompanied by simultaneous time-dependent accumulation of serum GH-BP.