Laron-type dwarfism is an autosomal recessive genetic disorder that is characterized by high levels of growth hormone and low levels of insulin-like growth factor I in the circulation. Several lines of evidence suggest that this disease is caused by a defect in the growth hormone receptor. In order to analyze the receptor gene in patients with Laron-

Serum growth hormone binding protein (GHBP) activity was estimated in healthy neonates (n = 6), children and adolescents (n = 97) and young adults (n = 19). GHBP activity was measured by incubating 125I-hGH (human growth hormone) (approximately 25,000 c.p.m.) with serum (100 microliters) in the presence and in the absence of excess unlabelled hGH, followed by separation of specifically bound 125I-hGHBP complexes from free 125I-hGH by gel filtration on Ultrogel AcA44 minicolumns. The results are expressed as the percentage specific binding relative to an adult reference serum (%RSB), after correction for endogenous hGH of the unknown serum. The between-assay coefficients of variation for two sera of %RSB activity of 51.2 and 115.4% were 6.0 and 7.0% respectively. In neonates, low values of serum GHBP were found (%RSB = 27.1 +/- 5.0 SEM) followed by a major rise during the first 6 years of life to a mean value (%RSB = 68.3 +/- 4.1 SEM) which more than doubled that of neonates. Thereafter, values rose progressively throughout childhood and puberty to reach maximum values in young adults (%RSB = 95.0 +/- 3.1 SEM). A novel observation was that serum GHBP activity correlated significantly with height standard deviation score (SDS) (males: r = 0.77, P less than 0.001; females: r = 0.56, P = 0.01) and weight SDS (P less than 0.001) for both sexes before puberty. During puberty GHBP correlated only with weight SDS in males (r = 0.60, P less than 0.01). In all age groups studied, no correlation could be found between serum GHBP and height velocity.

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...

The response of plasma hGH to an iv bolus injection of GRH1-44 (1 \g=m\g/kg) was studied in 14 obese juveniles with a mean overweight of 4.7 \ m=+-\0.05 standard deviation score (sds). Two patterns of response were observed: in all 7 adolescents with 'simple' obesity not related to any particular disorder (group A) the response was good (a mean of 11.8 \ m=+-\2.4 ng/ml) whereas in 6 of the 7 juveniles suffering from syndromes associated with obesity (group B) the response was poor (a mean of 3.2 \m=+-\1.4 ng/ml). This divergence in response could not be related to a difference in the degree of overweight. These results indicate that in group B with syndromes associated with obesity there may also be a pituitary impairment in addition to the hypothalamic defect.

The plasma LH, FSH and testosterone response to LRH was studied in 12 boys with compensatory testicular hypertrophy (CTH) and normal puberty and in a matched control group with normal testicular development. It was found, that the boys with CTH had normal basal plasma testosterone and LH concentrations; at the same time the basal plasma FSH level were significantly higher than in the control group. The response of plasma LH and FSH to LRH was markedly greater in the CTH group than it was in the control group. It is concluded, that the contralateral testicular hypertrophy which enables a normal pubertal process is the result of increased secretion of gonadotropins, mainly FSH.