A. Silbergeld

IGF binding protein 3 in patients with Laron type dwarfism: effect of exogenous rIGF‐I

objective The aim of the study was to investigate the serum levels of IGFBP‐3, the major IGF‐I binding protein, in patients with Laron type dwarfism (LTD) before and after IGF‐I treatment

Comparative effects of GH, IGF‐I and insulin on serum sex hormone binding globulin

OBJECTIVE The serum level of sex hormone binding globulin (SHBG) changes inversely with that of both insulin and Insulin‐like growth factor (IGF‐I), during several nutritional conditions, as well as In response to GH treatment. However, with exogenous IGF‐I administration, endogenous IGF‐I increases, while insulin decreases. In order to study the separate roles of these hormones in controlling SHBG metaboilsm, we compared SHBG levels in patients treated with IGF‐I and GH.

Patients with Laron syndrome have Osteopenia/Osteoporosis.

The paper, ‘‘Bone Mineral, Histomorphometry, and Body Composition in Adults with Growth Hormone Receptor Deficiency’’ by Bachrach et al. was of interest to us because our group has described the syndrome of growth hormone receptor deficiency (Laron syndrome [LS]). As agreed by international consensus, LS is a primary insulin-like growth hormone I (IGF-I) deficiency which, in addition to GH receptor defects, also comprises postreceptor defects with intact GH receptors. The above paper confirms and enlarges our previously published findings that patients with LS, from infancy, become progressively very obese, have thin bones, and, as adults, have osteoporosis, as evidenced by bone mineral density (BMD) examinations. These findings did not change during 9 months of treatment with daily IGF-I injections to adult patients. The changes during 7 years of treatment to children are being summarized at present. One year of treatment had no effect on BMD. The effects of long-term IGF-I treatment on serum procollagens in patients with LS, summarized separately, revealed that the initial, before treatment values in adult patients were lower than those in the children with LS and that all procollagen Type III (PIIINP), collagen I C-terminal telopeptide (ICTP), and procollagen I carboxy-terminal propeptide (PICP) levels rose in both patient populations during treatment. We thus concur with the above authors that IGF-I deficiency, whether primary or secondary, affects collagen tissues, but consider biochemical changes registered in all of our 49 patients, such as low serum P, alkaline phosphatase, and procollagens, X-rays of long bones and wrists over many years, and BMD by Lunar (DPX) as evidence for osteopenia/osteoporosis. Long-term treatment acts to reverse some of these pathological changes. REFERENCES

Serum prolactin in patients with Laron-type dwarfism : effect of insulin-like growth factor I

Prolactin (PRL) secretion was studied in Laron-type dwarfism (LTD) patients (8 children and 9 adults) in basal condition, after acute insulin-like growth factor (IGF-I) or TRH injections and during 2 months of daily IGF-I treatment. Basal PRL was repeatedly higher (12.6 +/- 1.6 micrograms/l) than that in control subjects (7.6 +/- 1.2 micrograms/l, p < 0.05). Acute IGF-I injection caused an immediate slight decrease in serum PRL and growth hormone (GH), followed by a progressive rise to mean peak levels of 33.3 +/- 4.5 micrograms/l again parallel to serum hGH which rose to 86 +/- 20 micrograms/l--a response to the IGF-I-induced hypoglycemia. Intravenous TRH in LTD children induced a marked response in serum PRL, similar to that registered in estrogenized adult females. Serum PRL did not show consistent changes during chronic IGF-I treatment. It is suggested that the higher-than-normal PRL levels and release in LTD patients are due to a drift phenomenon of the mammosomatotropes which produce large amounts of hGH.

The effect of normal human serum on proteoglycan synthesis

Abstract Embryonic chick cartilages were incubated with the radio-precursors 35 S, [ 3 H]glucosamine, [ 3 H]serine in the absence and presence of normal human serum in order to elucidate the steps in proteoglycan synthesis that are stimulated by normal serum. In the presence of serum there was similar increase in the uptake rates of all three precursors into both the entire tissue and isolated glycosaminoglycan chains which was proportional to the concentration of the serum. The effect of serum, cycloheximide, and D-xylose added separately and in various combinations was studied by following the distribution of 35 S-labelled macromolecules between tissue-bound and soluble fractions. The addition of serum alone led to a marked increaseof 35 S uptake in the tissue-bound fraction, whereas cycloheximide inhibited 35 S uptake into the tissue-bound fraction; however 35 S uptake into soluble fractions was unchanged for both additions. The introduction of D-xyclose to the incubation medium, led to a marked incrase in the soluble 35 S-labelled fraction with respect to the tissue-bound fraction, both with and without serum. The combination of cycloheximide and D-xyclose caused a further increase in the proportion of soluble/tissue-bound fractions. A comparison was made of the type of proteoglycan being synthesized in the presence of serum with that formed in its absence. Serum was found to stimulate proteoglycan with a higher protein content than that found in its absence. We conclude that serum stimulated the initial steps of proteoglycan synthesis either upon core-protein synthesis and/or its xylosylation, forming a slow diffusible product which is rapidly integrated into the tissue matrix.

Modulation of insulin like growth factor I (IGF-I) binding sites on erythrocytes by IGF-I treatment in patients with Laron syndrome (LS)

The in vivo regulation of IGF-I binding sites was evaluated using erythrocytes (RBC) from 8 patients with Laron syndrome (LS), before and after IGF-I treatment (120-150 micrograms/kg/day s.c.). Basal fasting IGF-I averaged 20.48 +/- 2.06 nmol/l (mean +/- S.E.M.) in the control group as compared to 4.72 +/- 0.84 nmol/l in the 8 LS patients (P = 0.0001). After 1 week of IGF-I treatment serum IGF-I levels increased to 6.53 +/- 1.58 nmol/l (a mean difference of 1.81 +/- 0.95, P = 0.05) and after 1 month of treatment to 14.37 +/- 4.56 nmol/l (a mean difference of 9.37 +/- 4.42, P = 0.03). Concomitantly, we found a significant decrease in the number of high affinity IGF-I binding sites, from 5.74 +/- 0.86 sites/cell (mean +/- S.E.M.) in the non-treated state to 2.29 +/- 0.64 sites/cell and 2.17 +/- 0.53 sites/cell after 1 week and 1 month of treatment, respectively (a mean difference of -3.44 +/- 0.94, P = 0.004 and -3.58 +/- 0.79, P = 0.002, respectively), values similar to those found in the control group. These data demonstrate that replacement treatment of LS patients with IGF-I down regulates its specific receptors. We propose IGF-I binding to RBC as a test to determine the responsiveness of patients considered for long term IGF-I treatment.

Modulation of IGF-I receptors by exogenous hGH treatment in constitutionally short children

OBJECTIVE To study the in‐vivo regulation of IGF‐I binding sites on erythrocytes (RBC) following administration of growth hormone (hGH) to constitutionally short children. Recently, owing to biosynthetic techniques, treatment with hGH has been administered not only to children with GH deficiency but also to children with constitutional growth delay and with familiaf short stature.