Growth hormone-releasing effect of oral growth hormone-releasing peptide 6 (GHRP-6) administration in children with short stature

1995 ◽  
Vol 133 (4) ◽  
pp. 425-429 ◽  
Author(s):  
J Bellone ◽  
L Ghizzoni ◽  
G Aimaretti ◽  
C Volta ◽  
MF Boghen ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Oral Administration ◽  
Short Stature ◽  
Area Under Curve ◽  
Low Dose ◽  
Height Velocity ◽  
Pubertal Stage ◽  
Gh Secretion ◽  
Short Children ◽  
Releasing Effect

Bellone J, Ghizzoni L, Aimaretti G, Volta C, Boghen MF, Bernasconi S, Ghigo E. Growth hormonereleasing effect of oral growth hormone-releasing peptide 6 (GHRP-6) administration in children with short stature. Eur J Endocrinol 1995;133:425–9. ISSN 0804–4643 Growth hormone-releasing peptide 6 (GHRP-6) is a synthetic hexapeptide with a potent GH-releasing activity after intravenous, subcutaneous, Intranasal and oral administration in man. Previous data showed its activity also in some patients with GH deficiency. The aim of our study was to verify the GH-releasing activity of oral GHRP-6 administration on GH secretion in children with normal short stature. The effect of oral GHRP-6 (300 μg/kg) was compared with that of the maximally effective dose of intravenous GH-releasing hormone (GHRH-29, 1 μg/kg). As the GHRH-induced GH rise in children is potentiated by arginine (ARG), even when administered by oral route at low dose (4 g), we studied also the interaction of oral GHRP-6 and ARG administration. We studied 13 children (nine boys and four girls aged 6.2–10.5 years, pubertal stage I) with normal short stature (height less than –2 sd score; height velocity more than –2 sd score; normal bone age; insulin-like growth factor I > 70 μg/l), In a first group of children (N = 7), oral GHRP-6 administration induced a GH response (mean ± sem, peak at 60 min vs baseline: 18.8 ±3.0 vs 1.1 ± 0.3 μg/l, p < 0.0006; area under curve: 1527.3 ± 263.9 μgl−1 h) which was similar to that elicited by GHRH (peak at 45 min vs baseline: 20.8 ±4.5 vs 2.2±0.9 μg/l, p <0.007; area under curve: 1429.4 ± 248.2 μgl−1 h−1). In a second group of children (N = 6), the GH response to oral GHRP-6 administration (peak at 75 min vs baseline: 18.5 ±5.1 vs 1.5 ± 0.6 μg/l, p < 0.01; area under curve: 1598.5 ± 289.3 μgl−1 h−1) was not modified by co-administration of oral ARG (peak at 90 min vs baseline: 15.2 ±5.6 vs 0.9±0.3 μg/l, p < 0.002; area under curve: 1327.8 ± 193.2 μgl−1 h−1). The amount of GH released and the timing of the somatotrope response after the oral administration of GHRP-6 were similar in the two groups. In conclusion, the present data show that in normal short children the oral administration of GHRP-6 is able to increase GH secretion to an extent similar to that observed after intravenous administration of the maximally effective GHRH dose. Moreover, in contrast to GHRH, the effect of GHRP-6 is not enhanced by low-dose oral ARG. As this amino acid likely acts via inhibition of hypothalamic somatostatin release, our data suggest that a decrease in the somatostatinergic activity does not improve the GH-releasing effect of GHRP-6 in childhood, at variance with that observed after GHRH. Our results suggest that GHRP-6 could be clinically useful to stimulate GH secretion in short children. E Ghigo, Divisione di Endocrinologia, Ospedale Molinette, C. so. AM Dogliotti 14, 10126 Torino, Italy

Growth hormone-releasing peptides

1997 ◽  
Vol 136 (5) ◽  
pp. 445-460 ◽  
Author(s):  
E Ghigo ◽  
E Arvat ◽  
G Muccioli ◽  
F Camanni
Keyword(s):  
Growth Hormone ◽  
Oral Administration ◽  
Height Velocity ◽  
Age Related ◽  
Short Children ◽  
Opioid Receptor Antagonists ◽  
Growth Hormone Releasing Peptides ◽  
Releasing Effect ◽  
Hypothalamic Level

Abstract Growth hormone-releasing peptides (GHRPs) are synthetic, non-natural peptides endowed with potent stimulatory effects on somatotrope secretion in animals and humans. They have no structural homology with GHRH and act via specific receptors present either at the pituitary or the hypothalamic level both in animals and in humans. The GHRP receptor has recently been cloned and, interestingly, it does not show sequence homology with other G-protein-coupled receptors known so far. This evidence strongly suggests the existence of a natural GHRP-like ligand which, however, has not yet been found. The mechanisms underlying the GHRP effect are still unclear. At present, several data favor the hypothesis that GHRPs could act by counteracting somatostatinergic activity both at the pituitary and the hypothalamic level and/or, at least partially, via a GHRH-mediated mechanism. However, the possibility that GHRPs act via an unknown hypothalamic factor (U factor) is still open. GHRP-6 was the first hexapeptide to be extensively studied in humans. More recently, a heptapeptide, GHRP-1, and two other hexapeptides, GHRP-2 and Hexarelin, have been synthesized and are now available for human studies. Moreover, non-peptidyl GHRP mimetics have been developed which act via GHRP receptors and their effects have been clearly demonstrated in animals and in humans in vivo. Among non-peptidyl GHRPs, MK-0677 seems the most interesting molecule. The GH-releasing activity of GHRPs is marked and dose-related after intravenous, subcutaneous, intranasal and even oral administration. The effect of GHRPs is reproducible and undergoes partial desensitization, more during continuous infusion, less during intermittent administration; in fact, prolonged administration of GHRPs increases IGF-I levels both in animals and in humans. The GH-releasing effect of GHRPs does not depend on sex but undergoes age-related variations. It increases from birth to puberty, persists at a similar level in adulthood and decreases thereafter. By the sixth decade of life, the activity of GHRPs is reduced but it is still marked and higher than that of GHRH. The GH-releasing activity of GHRPs is synergistic with that of GHRH, is not affected by opioid receptor antagonists, such as naloxone, and is only blunted by inhibitory influences, including neurotransmitters, glucose, free fatty acids, glucocorticoids, recombinant human GH and even exogenous somatostatin, which are known to almost abolish the effect of GHRH. GHRPs maintain their GH-releasing effect in somatotrope hypersecretory states such as in acromegaly, anorexia nervosa and hyperthyroidism. On the other hand, their good GH-releasing activity has been shown in some but not in other somatotrope hyposecretory states. In fact, reduced GH responses after GHRP administration have been reported in idiopathic GH deficiency as well as in idiopathic short stature, in obesity and in hypothyroidism, while in patients with pituitary stalk disconnection or Cushing's syndrome the somatotrope responsiveness to GHRPs is almost absent. In short children an increase in height velocity has also been reported during chronic GHRP treatment. Thus, based on their marked GH-releasing effect even after oral administration, GHRPs offer their own clinical usefulness for treatment of some GH hyposecretory states. European Journal of Endocrinology 136 445–460

scholarly journals Urinary Growth Hormone Excretion as Measured by a Sensitive Immunochemiluminometric Assay

1993 ◽  
Vol 30 (2) ◽  
pp. 180-185 ◽  
Author(s):  
G Turner ◽  
R C Brown ◽  
I Weeks ◽  
G E Butler ◽  
F N Creagh ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Individual Variability ◽  
Height Velocity ◽  
Growth Disorders ◽  
Serum Growth Hormone ◽  
Renal Handling ◽  
Gh Secretion ◽  
Normal Stature ◽  
Optimum Sampling

A sensitive immunochemiluminometric assay with a detection limit of 1 · 1μU/L was developed for the measurement of urinary growth hormone (UGH). The assay was shown to be specific and precise. There was a good correlation between serum growth hormone (GH) and UGH concentrations in 20 patients with acromegaly and six volunteers following an intravenous injection of recombinant GH. We concluded therefore that UGH measurements appear to provide a satisfactory index of GH secretion. The use of the assay in the investigation of growth disorders was assessed. We studied 11 pre-pubertal children, six of normal stature, and five of short stature, over a 6-month period. Sequential fortnightly measurements of UGH were carried out and height velocity was determined. The children of short stature grew at a slower rate and excreted less GH than the children of normal stature. However, we observed considerable within-individual variability in GH excretion in both groups (CV 22–98%). We therefore recommend that sequential UGH analyses should be carried out and the results interpreted in conjunction with growth measurements. However, further investigations into the renal handling of GH are needed to establish optimum sampling regimes.

Genetic defects causing functional and structural isolated growth hormone deficiency

2011 ◽  
Vol 2 (2) ◽  
Author(s):  
Vibor Petkovic ◽  
Primus Mullis
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Somatic Growth ◽  
Human Growth ◽  
Postnatal Growth ◽  
Metabolic Effects ◽  
Hormone Deficiency ◽  
Height Velocity ◽  
Gh Secretion ◽  
Normal Standards

AbstractNormal somatic growth requires the integrated function of many of the hormonal, metabolic, and other growth factors involved in the hypothalamo-pituitary-somatotrope axis. Human growth hormone (hGH) causes a variety of physiological and metabolic effects in humans and its pivotal role in postnatal growth is undisputed. Disturbances that occur during this process often cause subnormal GH secretion and/or subnormal GH sensitivity/responsiveness resulting in short stature. Despite the complexity of this linear growth process, the growth pattern of children, if evaluated in the context of normal standards, is rather predictable. Children presenting with short stature (i.e out of normal standards) are treated with daily injections of recombinant human GH (rhGH), which leads in almost all cases to an increase of height velocity. Although it is becoming more and more evident that many genes are involved in controlling the regulation of growth, the main aim of this review is to focus on the GH-1 gene, the various gene alterations and their important physiological and pathophysiological role in growth.

Growth hormone secretion in patients with Turner's syndrome as determined by time series analysis

1992 ◽  
Vol 127 (1) ◽  
pp. 7-12 ◽  
Author(s):  
Jan M Wit ◽  
Albert A Massarano ◽  
Gerdine A Kamp ◽  
Peter C Hindmarsh ◽  
An van Es ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Ethinyl Estradiol ◽  
Height Velocity ◽  
Breast Development ◽  
Turner's Syndrome ◽  
Turner’S Syndrome ◽  
Estradiol Treatment ◽  
Gh Secretion ◽  
Short Children ◽  
Significant Difference

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.

The Role of Auxologic and Growth Factor Measurements in the Diagnosis of Growth Hormone Deficiency

PEDIATRICS ◽  
1998 ◽  
Vol 102 (Supplement_3) ◽  
pp. 524-526
Author(s):  
Raymond L. Hintz
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Growth Hormone Deficiency ◽  
Short Stature ◽  
The Body ◽  
Hormone Deficiency ◽  
Insulin Like Growth Factor ◽  
Growth Study ◽  
Short Children ◽  
National Cooperative

The use of auxologic measurements in the diagnosis of short stature in children has a long history in pediatric endocrinology, and they have even been used as the primary criteria in selecting children for growth hormone (GH) therapy. Certainly, an abnormality in the control of growth is more likely in short children than in children of normal stature. However, most studies have shown little or no value of auxologic criteria in differentiating short children who have classic growth hormone deficiency (GHD) from short children who do not. In National Cooperative Growth Study Substudy VI, in more than 6000 children being assessed for short stature, the overall mean height SD score was −2.5 ± 1.1 and the body mass index standard deviation score was −0.5 ± 1.4. However, there were no significant differences in these measures between the patients who were found subsequently to have GHD and those who were not. There also was no consistent difference in the growth rates between the patients with classic GHD and those short children without a diagnosis of GHD. This probably reflects the fact that we are dealing with a selected population of children who were referred for short stature and are further selecting those who are the shortest for additional investigation. Growth factor measurements have been somewhat more useful in selecting patients with GHD and have been proposed as primary diagnostic criteria. However, in National Cooperative Growth Study Substudy VI, only small differences in the levels of insulin-like growth factor I and insulin-like growth factor binding protein 3 were seen between the patients who were selected for GH treatment and those who were not. Many studies indicate that the primary value of growth factor measurements is to exclude patients who are unlikely to have GHD or to identify those patients in whom an expedited work-up should be performed. The diagnosis of GHD remains difficult and must be based on all of the data possible and the best judgment of an experienced clinician. Even under ideal circumstances, errors of both overdiagnosis and underdiagnosis of GHD still are likely.

Treatment of Short Stature in Aggrecan Deficient Patients with Recombinant Human Growth Hormone: One-Year Response

2021 ◽  
Author(s):  
Gajanthan Muthuvel ◽  
Andrew Dauber ◽  
Eirene Alexandrou ◽  
Leah Tyzinski ◽  
Melissa Andrew ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Human Growth Hormone ◽  
Linear Growth ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Skeletal Maturation ◽  
Height Velocity ◽  
Heterozygous Mutation ◽  
One Year

Abstract Context Patients with aggrecan (ACAN) deficiency present with dominantly inherited short stature, often with advanced skeletal maturation and premature growth cessation. There is a paucity of information on the effects of growth-promoting interventions. Objective The aim of this study was to evaluate the efficacy and safety of recombinant human growth hormone (rhGH) therapy on linear growth in children with ACAN deficiency. Design and Setting Open-label, single-arm, prospective study at Cincinnati Children’s Hospital Medical Center. Patients Ten treatment-naïve patients were recruited. Inclusion criteria were: a confirmed heterozygous mutation in ACAN, age ≥ 2 years, pre-pubertal, bone age (BA) ≥ chronological age (CA), and normal IGF-I concentration. Intervention Treatment with rhGH (50 mcg/kg/day) over one year. Main Outcome Measure(s) Main outcomes measured were height velocity (HV) and change in (Δ) height SD (HtSDS). Results Ten patients (six females) were enrolled with median CA of 5.6 yrs (range 2.4 to 9.7). Baseline median HtSDS was -2.5 (range -4.3 to -1.1). Median baseline BA was 6.9 yrs (range 2.5 to 10.0), with median BA/CA of 1.2 (range 0.9 to 1.5). Median pre-treatment HV was 5.2 cm/y (range 3.8 to 7.1), increased to 8.3 cm/y (range 7.3 to 11.2) after one year of therapy (p=0.004). Median ΔHtSDS after one year was +0.62 (range +0.35 to +1.39) (p=0.002). Skeletal maturation did not advance inappropriately (median Δ BA/CA -0.1, p=0.09). No adverse events related to rhGH were observed. Conclusion Treatment with rhGH improved linear growth in a cohort of patients with short stature due to ACAN deficiency.

Short Children and Growth Hormone

PEDIATRICS ◽  
1984 ◽  
Vol 73 (1) ◽  
pp. 112-113
Author(s):  
KENNETH C. COPELAND
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Growth Rates ◽  
Plasma Concentrations ◽  
Normal Growth ◽  
Somatomedin C ◽  
Short Children ◽  
Provocative Testing

To the Editor.— The article by Bright et al1 was a provocative description of two subjects with short stature, normal growth hormone (GH) responses to provocative testing, and low somatomedin-C (SM-C) concentrations, which increased after administration of GH. The authors conclude that the short stature in these individuals may be due to a biologically inactive GH molecule or to decreased dose responsiveness to GH of SM-producing cells. Their data also seem compatible with a third possibility: normal short children respond to GH administration with increases in SM-C plasma concentrations and growth rates.

Standard and low-dose IGF-I generation tests and spontaneous growth hormone secretion in children with idiopathic short stature

2004 ◽  
Vol 60 (2) ◽  
pp. 163-168 ◽  
Author(s):  
J. C. Blair ◽  
C. Camacho-Hübner ◽  
F. Miraki Moud ◽  
S. Rosberg ◽  
C. Burren ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Low Dose ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Idiopathic Short Stature ◽  
Spontaneous Growth ◽  
Igf I

Effects of glucocorticoid treatment and acute passive immunization with growth hormone-releasing hormone and somatostatin antibodies on endogenous and stimulated growth hormone secretion in the male rat

1991 ◽  
Vol 131 (1) ◽  
pp. 75-86 ◽  
Author(s):  
J. Miell ◽  
R. Corder ◽  
P. J. Miell ◽  
C. McClean ◽  
R. C. Gaillard
Keyword(s):  
Growth Hormone ◽  
Low Dose ◽  
Growth Hormone Secretion ◽  
Blood Sampling ◽  
Male Rat ◽  
High Dose ◽  
Glucocorticoid Treatment ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Medium Dose

ABSTRACT Despite causing marked inhibition of somatic growth, glucocorticoids enhance both the response to GH-releasing hormone (GHRH) and the amplitude of naturally occurring GH secretory pulses in the male rat. The relative contribution of the two major hypothalamic regulatory factors for GH (somatostatin and GHRH) to these observed effects remains speculative. In the present studies, we have investigated endogenous and stimulated GH release in rats pretreated with glucocorticoid or vehicle, and the effects of passive immunoneutralization of somatostatin or GHRH. In an initial study, four groups of eight rats were treated with either saline or various doses of a depot preparation of betamethasone: low dose, 0·85 mg; medium dose, 1·7 mg; high dose, 3·4 mg. All doses significantly suppressed body weight gain, total adrenal weight and concentrations of both plasma corticosterone and pituitary ACTH. Seven days after betamethasone treatment, GH responses to an i.v. injection of 1 μg human GHRH(1–29) were evaluated during pentobarbitone anaesthesia. Compared with saline-treated controls (peak GH concentration of 506·0±68·5 μg/l), peak GH levels were enhanced by the low dose (704·4±47·8 μg/l, P<0·05), unaltered by the medium dose (543±65·8 μg/l) and suppressed by the high dose (312·7±55·2 μg/l, P<0·05) of betamethasone. Similarly, the area under the secretory curves was increased by 46% following the low dose (P<0·01), unaltered by the medium dose and reduced by 33% after the high dose of betamethasone. In a second study, rats were pretreated for 7 days before blood sampling with either the medium dose of betamethasone or saline. On day 5, 48 h before blood sampling, an indwelling venous catheter was fitted enabling sampling of conscious rats. On the day of study, blood samples were taken at 30-min intervals over an initial 2-h period (10.00–12.00 h). Following the sample at 12.00 h, rats were given the reconstituted and dialysed immunoglobulin fraction from either control sheep serum (NSIgG), sheep anti-rat GHRH serum (GHRHab) or sheep anti-somatostatin serum (SRIHab), and samples were taken for a further 90 min (12.30–14.00 h). Directly after the sample at 14.00 h, GH stimulation was effected in all rats using 1 μg human GHRH(1–29) with samples taken at 5, 10, 20 and 40 min following stimulation. During the initial sampling period, mean GH levels were significantly (P<0·005) higher in steroidpretreated animals than in saline-pretreated controls (29·3±5·8 vs 13·2±1·6 μg/l), with a higher amplitude secretory pulse occurring at 11.30 h (80·7±18·6 vs 26·4±4·1 μg/l, P < 0·01). Administration of GHRHab to saline-pretreated animals did not alter mean GH levels when compared with animals receiving control NSIgG (saline plus NSIgG, 9·3±1·1; saline plus GHRHab, 8±1·1 μg/l, P = NS). In contrast, the raised mean GH levels seen in betamethasone-pretreated rats receiving NSIgG (12·3 ±1·1 μg/l) were reduced by GHRHab administration (7·6±1·1 μg/l); these levels were not different from those of the saline-pretreated group suggesting that the observed permissive effect of glucocorticoids on GH secretion is mediated through enhanced GHRH activity. SRIHab increased mean basal GH levels to a similar extent in both saline- and betamethasone-pretreated groups (17·4±1·2 μg/l and 19·3 ±1·1 μg/l respectively, P<0·01 vs comparable NSIgG group). Administration of the various immunoglobulin fractions had no effect on GHRH-stimulated GH secretion except when SRIHab was given to betamethasone-pretreated animals, resulting in a significantly increased peak response (1467±93 μg GH/l, P<0·001) when compared with either saline- or betamethasone-pretreated rats given NSIgG (643±95 and 791±92 μg/l respectively). This enhancement following SRIHab administration was not seen in saline-pretreated animals (893±180 μg GH/l). These results imply that glucocorticoid treatment increases basal GH levels through a GHRH-dependent mechanism and also increases pituitary sensitivity to exogenous GHRH when inhibitory somatostatin tone is blocked. Journal of Endocrinology (1991) 131, 75–86

A possible relationship between serum transferrin, growth hormone secretion and height velocity in children

1980 ◽  
Vol 93 (2) ◽  
pp. 134-138 ◽  
Author(s):  
M. Donnadieu ◽  
R. M. Schimpff ◽  
P. Garnier ◽  
J. L. Chaussain ◽  
J. C. Job
Keyword(s):  
Growth Hormone ◽  
Growth Regulation ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Height Velocity ◽  
Obese Children ◽  
Gh Secretion ◽  
Growth Promoting

Abstract. Since transferrin (Tf) in vitro has a growth-promoting activity and is associated with NSILA properties, the aim of this work was to study in vivo the relationships between Tf, somatomedin activity (SM), growth hormone (GH) secretion, and height velocity in children. An iv infusion of ornithine hydrochloride was given to 23 controls; the induced rise of GH was accompanied by a simultaneous fall of SM (r = −0.711, P < 0.001) and was preceded by a fall of Tf (r = −0.610, P < 0.01). In 17 obese children SM was within the normal range, when Tf levels were higher and arginineinduced GH peaks lower than in the controls, and a negative correlation was found between Tf basal levels and GH peaks (r = −0.608, P < 0.01). In 9 children with confirmed hypopituitarism the Tf levels were significantly lower than in the controls. In 14 children with confirmed or suspected hypopituitarism a single im injection of hGH (6 mg) failed to induce Tf variations over 24 h. In 39 of these children the height velocity was significantly correlated with Tf basal levels (r = 0.701, P < 0.001). These data suggest that transferrin is involved in growth regulation, and that GH secretion is related to transferrin levels by a feed-back mechanism.

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