The heptapeptide growth hormone-releasing peptide-1 (GHRP-1 ), one of a series of recently synthesized small growth hormone (GH)-releasing peptides, was administered as an iv bolus (1 \g=m\g/kg) to 15 (six prepubertal, nine pubertal) short but healthy children and adolescents and to eight juvenile patients with pituitary insufficiency (four with isolated growth hormone deficiency, two with multiple pituitary hormone deficiencies, one with partial GH deficiency and one with GH-releasing hormone (GHRH) deficiency). Eleven out of 23 subjects also underwent an iv GHRH (1\p=n-\29) test (1 \g=m\g/kg). All the healthy children responded with a progressive rise in plasma human GH (hGH) peaking at 15\p=n-\30min, with a significantly higher rise (p<0.05) in the pubertal than prepubertal group. The hGH response to GHRH (1\p=n-\29) in these children was similar or slightly higher. Six hypopituitary patients had no response to either GHRP-1 or GHRH; the patient with partial GH deficiency had a hGH peak of 6.5 \g=m\g/l(at 5 min) to GHRP-1 and 9.2 \g=m\g/l(at 1 5 min) to GHRH. One patient had no response of hGH to hypoglycemia, clonidine and GHRP-1, but the plasma hGH rose to 10 \g=m\g/l after GHRH. Following the GHRP-1 bolus there was a significant (p <0.01) rise in plasma free thyroxine and a decrease of thyrotropin (p <0.01), both in the limits of normal values. There was also a transitory rise of plasma cortisol (p <0.05). Plasma prolactin, luteinizing hormone and follicle-stimulating hormone did not change. It is concluded that GHRP-1 is a potent GH-releasing drug because it acts also when administered orally and has great pharmaceutical and clinical applications.In recent years a series of small GH-releasing peptides (GHRPs) have been synthesized. These peptides consist of six or seven amino acids and have been found specifically to release GH in several animal species as well as in man (1, 2). So far, three GHRPs have been tried in man (GHRP-1, GHRP-6 and recently GHRP-2) and, interestingly, they release hGH not only after intra¬ venous or subcutaneous injection but also after oral ingestion (3,4). It has been claimed that in normal adult men the GHRPs release hGH more effectively than GHRH (1-44) (2). As there are only two previous reports on the effect of CHRP in a relatively small number of children (5, 6), we extended this experience to children and adolescents with known normal or abnormal GH secretion. Subjects and methodsFifteen children with normal and eight with abnormal hGH secretion were included in the study. The 15 children with normal hGH secretion (constitutional short stature) comprised six prepubertal (4M, 2F) chil¬ dren of mean age 9.4±0.45 (sem) years and nine pubertal (7M, 2F) children of mean age 15.4±0.45 years. The all-male group of hypopituitary patients with abnormal hGH secretion consisted of six patients aged 18.3 ± 1.2 years with hGH deficiency of pituitary origin (four with isolated GH deficiency and two with multiple pituitary hormone deficiencies), one aged 14 years with partial GH deficien...

We have investigated the largest family with PROP1 deficiency reported to date. Eight patients, aged 17-40 yr, in two sibships with possibly related mothers but no parental consanguinity were 109 -137 cm in height (Ϫ8.8 to [minsu]5.9 SD score) and sexually immature. None had received hormonal therapy. Affected individuals had similarities to and significant differences from patients with insulin-like growth factor I (IGF-I) deficiency due to GH receptor deficiency (GHRD) and normal thyroid function and sexual maturation. The differences from patients with GHRD include normal hand and foot length in seven of eight, normal arm span with relatively long legs, and persistence of extremely low levels of IGF-I into adulthood; similarities include the degree of growth failure, frequent but not uniform increased body weight for height or body mass index, and the presence of limited elbow extensibility and blue scleras in six of eight. Three patients had markedly increased sella turcica area for height age and bone age, determined from lateral skull films. The degree of sellar enlargement is variable in these two sibships.Serum GH concentrations were 0.1 ng/mL or less after clonidine ingestion. Other results were: IGF-I, 3-11 ng/mL (normal, 114 -492); IGF-II, 185-299 ng/mL (normal, 358 -854); IGF-binding protein-1 (IGFBP-1), 12-200 ng/mL (normal, 13-73); IGFBP-2, 60 -384 ng/mL (normal, 55-480); and IGFBP-3, 400 -600 ng/mL (normal, 2000 -4000). The very low IGF-I and normal IGFBP-1 and -2 levels differ from findings in adults with GHRD. The GH-binding protein concentration was 58 -799 pmol/L, with two patients above the normal range of 66 -306. LH and FSH levels were very low, with no sex differences between serum levels of estradiol (3-6 pg/mL) and testosterone (3-10 ng/dL). PRL levels all were below normal. Serum concentrations of cortisol were normal. Serum T 4 levels were uniformly low (Ͻ0.2-0.5; normal, 0.8 -2.7 ng/dL), free T 3 values were less than normal in seven of eight subjects, and total T 3 concentrations were below normal in five of eight, but TSH levels were normal (0.58 -2.18; normal, 0.4 -4.2 mU/L).DNA specimens from affected individuals in each sibship were homozygous for a 2-bp deletion in exon 2 of the PROPI (Prophet of Pit-I) gene, which causes a shift of reading frames and results in a translational stop signal at codon 109. The mutant protein, when expressed in vivo lacks DNA-binding and transcriptional activation functions. The consequences of the PROPI abnormality in this and other kindreds include gonadotropin deficiency as well as the expected deficiencies in products of Pit-I-dependent somatotrophs, lactotrophs, and thyrotrophs. The severity of the hormone deficiency phenotype is compatible with the complete loss of PROP1 activity. (J Clin Endocrinol Metab 84: 50 -57, 1999)

Three Laron Syndrome (LS) siblings with a post growth hormone (GH) receptor defect for insulin-like growth factor-I (IGF-I) synthesis were found to have serum GH-binding protein (GHBP) levels normal for age. Treatment with recombinant IGF-I (150 micrograms/kg/day) decreased serum GHBP activity to 62% of the basal value (P < 0.001) in two of the sibs in 1 week and in the third sib after 3 months of therapy. Scatchard analysis of the binding of [125I]human GH (hGH) to GHBP in patients' sera before and during therapy revealed affinity constants Ka = 1.55-1.80 x 10(9) M-1, similar to that of sera from healthy subjects. Variations in binding are due to changes in the binding capacity. IGF-I may be a regulatory factor for serum GHBP activity in man.