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Helen A Spoudeas, Andy P Winrow, Peter C Hindmarsh and Charles GD Brook

Spoudeas HA, Winrow AP, Hindmarsh PC, Brook CGD. Low-dose growth hormone-releasing hormone tests: a dose-response study. Eur J Endocrinol 1994;131:238–45. ISSN 0804–4643

We have evaluated parameters of the serum growth hormone (GH) concentration response to saline and 1-, 10- and 100-μg intravenous bolus doses of amide analogue of GH-releasing hormone (GHRH (1–29)NH2) given in random order to 10 adult male volunteers of median body weight 68 (60–90)kg. Compared with saline, both 10- and 100-μg GHRH(1–29)NH2 doses (but not 1 μg) resulted in significant peak GH responses (means and 95% confidence intervals: 24.03 (11.22–51.29) vs 26.09 (16.40–41.50) mU/l, respectively). Although the average rate of serum GH rise was similar after both 10 μg (2.05 (1.13–2.97) mU · l−1 · min−1) and 100 μg of GHRH(1–29)NH2 (1.52 (0.69–2.35) mU·1−1 · min−1; ANOVA F = 0.93, p = 0.35), the average rate of serum GH decline after peak GH was slower after the higher dose (10 μg vs 100 μg: 0.65 (0.40–0.90) vs 0.37 (0.23–0.50) mU·1−1·min−1; ANOVA F = 5.14, p = 0.04), suggesting continued GH secretion. Increasing GHRH(1–29)NH2 doses delayed the time to peak GH (1 μg: 7.00 (3.50–10.52) min; 10 μg: 15.80 (13.62–17.98) min; 100 μg: 24.80 (18.40–31.12) min) and serum GH levels were still elevated significantly 2 h after injection of 100 μg GHRH(1–29)NH2 compared with other doses (saline: 0.98 (0.48–2.04) mU/1; 1 μg: 0.68 (0.48–0.93) mU/1; 10 μg: 1.07 (0.56–2.04) mU/1; 100 μg: 5.01 (2.34–10.86) mU/l; ANOVA F = 11.10, p < 0.001). In a second study we tested five adult male volunteers with lower doses (0.5–10 μg) of GHRH(1–29)NH2. Consistent responses were observed only at doses equal to or greater than 2.5 μg and all occurred between 10 and 25 min. The estimated ed50 for GHRH(1–29)NH2 from the combined study data was 7.5 μg (0.08 μg/kg; range 0.06–0.12 μg/kg). The 10-μg dose of GHRH(1–29)NH2 was a maximal stimulus in all release parameters examined and GH peaks of < 15 mU/l (10th centile) should be considered potentially abnormal. Lower doses of GHRH(1–29)NH2 released GH quicker than higher doses, which simply prolonged the response, possibly by causing release from different pools. Our results suggest that sampling at 0, 10, 15, 20 and 25 min after a 10-μg dose of GHRH(1–29)NH2 will identify all GH peaks.

CGD Brook, The Endocrine Unit, Middlesex Hospital, Mortimer Street, London WIN 8AA, UK

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Jan M Wit, Albert A Massarano, Gerdine A Kamp, Peter C Hindmarsh, An van Es, Charles GD Brook, Michael A Preece and David R Matthews

Twenty-four-hour growth hormone (GH) profiles in 26 girls with Turner's syndrome were compared with those of 26 normally growing short children and 24 slowly growing short children. All children were prepubertal and below 12 years of age. A subgroup of 13 girls was treated with ethinyl estradiol and a 24-h GH profile was reassessed. In an additional group of 45 girls with Turner's syndrome (aged 6.7–18.9 years) the effect of age, spontaneous breast development and ethinyl estradiol treatment was studied. The profiles were assessed by Fourier analysis. The oscillatory activity and the mean 24-h GH concentration were similar in children with Turner's syndrome and the normally growing short children, in contrast to lower levels in the slowly growing short children. The periodicity of GH secretion was similar in all groups. In the longitudinal study, ethinyl estradiol treatment resulted in a significant increase in pulse amplitude, but not in periodicity. In the cross-sectional study there was no significant difference between the subgroups of girls with either presence or absence of breast development or ethinyl estradiol treatment. GH secretion was not significantly related to age, height in standard deviation score or height velocity. These data imply that there is no abnormality in GH secretion in girls with Turner's syndrome.

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Mehul T Dattani, Andrew P Winrow, Anatoly Tuil'Pakov, P Jane Pringle, Peter C Hindmarsh, Charles GD Brook and Nicholas J Marshall

Dattani MT, Winrow AP, Tuil'Pakov A, Pringle PJ, Hindmarsh PC, Brook CGD, Marshall NJ. Evaluation of growth hormone (GH) responses to pulsed GH-releasing hormone administration using the MTT–ESTA bioassay. Eur J Endocrinol 1996;135:87–95. ISSN 0804–4643

We compared the immunoactivity of human growth hormone (hGH) with its bioactivity after stimulation of hGH release into the circulation by the administration of growth hormone-releasing hormone [GHRH(1–29)-NH2] according to a pre-determined protocol to four normal adult volunteers. We used the Hybritech immunoradiometric assay to measure the immunoactive GH concentrations. Bioactive GH concentrations were measured using the highly quantitative and precise eluted stain bioassay system (ESTA). The high sample capacity of the ESTA bioassay permitted us to monitor the bioactivities in closely timed sequential samples, and in far greater detail than has previously been possible. Two pulses of GHRH(1–29)-NH2 were administered intravenously to the four adult male volunteers (aged 24–37 years) on a weekly basis over a 4-week period. Two different doses of GHRH(1–29)-NH2 (0.1 and 1.0 μg/kg) were tested. These were separated by specified time intervals (60 or 120 min). Responses in the four individuals were variable. However, although the immunoand bioactivities generally agreed well, there was a systematic and progressive increase in the bioactivity/immunoactivity (B/I) ratios as half of the response peaks were approached. After these peak concentrations, the B/I ratios subsequently returned to values that were close to unity. The enhanced bioactivity of the peak samples from the two volunteers in whom the largest magnitudes of response were observed was found to be labile after long-term storage at −20°C. We suggest that the preferential rise in GH bioactivity, as opposed to immunoactivity, in response to GHRH(1–29)-NH2 was due to progressive changes in the concentrations of isoforms of GH that are not detectable in the Hybritech immunoassay.

NJ Marshall, Division of Molecular Pathology, University College London, The Windeyer Building, 46 Cleveland Street, London W1P 6DB, UK