LOW-DOSE GROWTH HORMONE-RELEASING HORMONE TESTS - A DOSE-RESPONSE STUDY

We have evaluated parameters of the serum growth hormone (GH) concentr ation response to saline and 1-, 10- and 100-mu g intravenous bolus do ses of amide analogue of GH-releasing hormone (GHRH (1-29)NH2) given i n random order to 10 adult male volunteers of median body weight 68 (6 0-90)kg. Compared with saline, both 10- and 100-mu g GHRH(1-29)NH2 dos es (but not 1 mu g) resulted in significant peak GH responses (means a nd 95% confidence intervals: 24.03 (11.22-51.29) vs 26.09 (16.40-41.50 ) mU/1, respectively) Although the average rate of serum GH rise was s imilar after both 10 mu g 12.05 (1.13-2.97) mU.l(-1).min(-1) and 100 m u g of GHRH(1-29)NH2 (1.52 (0.69-2.35) mU.l(-1). min 1; ANOVA F = 0.93 , p = 0.35), the average rate of serum GH decline after peak GH was sl ower after the higher dose (10 mu g vs 100 mu g: 0.65 (0.40-0.90) vs 0 .37 (0.23-0.50) mU.l(-1) . min(-1); ANOVA F = 5.14, p = 0.04), suggest ing continued GH secretion. Increasing GHRH(1-29)NH2 doses delayed the time to peak GH (1 mu g: 7.00 (3.50-10.52) min; 10 mu g: 15.80 (13.62 -17.98) min; 100 mu g: 24.80 (18.40-31.12) min) and serum GH levels we re still elevated significantly 2 h after injection of 100 mu g GHRH(1 -29)NH2 compared with other doses (saline: 0.98 (0.48-2.04) mU/1; 1 mu g: 0.68 (0.48-0.93) mU/1; 10 mu g: 1.07 (0.56-2.04) mU/1; 100 mu g: 5 .01 (2.34-10.86) mU/1; ANOVA F = 11.10, p < 0.001). In a second study we tested five adult male volunteers with lower doses (0.5-10 mu g) of GHRH(1-29)NH2. Consistent responses were observed only at doses equal to or greater than 2.5 mu g and all occurred between 10 and 25 min. T he estimated ED(50) for GHRH(1-29)NH2 from the combined study data was 7.5 mu g (0.08 mu g/kg; range 0.06-0.12 mu g/kg). The 10-mu g dose of GHRH(1-29)NH2 was a maximal stimulus in all release parameters examin ed and GH peaks of < 15 mU/l (10th centile) should be considered poten tially abnormal. Lower doses of GHRH(1-29)NH2 released GH quicker than higher doses, which simply prolonged the response, possibly by causin g release from different pools. Our results suggest that sampling at 0 , 10, 15, 20 and 25 min after a 10-mu g dose of GHRH(1-29)NH2 will ide ntify all GH peaks.