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A Silbergeld

Publications and source records attributed to A Silbergeld.

At least 19 recordsLinked to original sources
PubMed2001

A novel somatostatin analogue prevents early renal complications in the nonobese diabetic mouse.

BACKGROUND: PTR-3173 (S) is a novel somatostatin analogue that has been found to exert a prolonged inhibitory action on the growth hormone (GH)-insulin-like growth factor (IGF)-I axis, but not on insulin secretion. We investigated the potential effect of this agent on the development of markers of diabetic nephropathy in the nonobese diabetic (NOD) mouse model of insulin-dependent diabetes. METHODS: Female diabetic NOD mice treated with PTR-3173 (DS group) or saline (D) and their control groups of nonhyperglycemic age-matched littermates (C) and C mice treated with PTR-3173 (CS) were sacrificed three weeks after onset of diabetes. RESULTS: Serum GH was elevated in the D group, decreased in the DS group, and unchanged in the CS group. Serum IGF-I was significantly decreased in both the D and DS groups. Kidney weight, glomerular volume, albuminuria, and creatinine clearance were increased in the D animals and showed a trend toward normalization in the DS animals. Renal extractable IGF-I protein and IGFBP1 mRNA were increased in the D group and normalized in the DS group. CONCLUSIONS: GH antagonism by PTR-3173 has a blunting effect on renal/glomerular hypertrophy, albuminuria, and glomerular filtration rate (GFR) in diabetic NOD mice. This phenomenon is apparently associated with the prevention of renal IGF-I accumulation. Thus, modulation of GH effects may have beneficial therapeutic implications in diabetic nephropathy.

Albuminuria↗
PubMed1998

Development of hyperandrogenism during treatment with insulin-like growth factor-I (IGF-I) in female patients with Laron syndrome.

OBJECTIVE: Patients with Laron syndrome (LS) can now be treated with recombinant IGF-I. We describe the development of androgenization during IGF-I treatment of female LS patients. PATIENTS: Six female patients with LS--two clinically prepubertal (11.6 and 13.8 years of age) and four young adults (30 to 39 years old)--underwent long-term replacement treatment with recombinant IGF-I. The daily doses were 150 micrograms/kg/day by subcutaneous (s.c.) injection in the girls and 120 micrograms/kg/day in the adult women. METHODS: Testosterone, delta 4-androstenedione, LH, FSH, insulin and IGF-I were determined by radioimmunoassay. Blood samples were obtained after an overnight fast before the IGF-I injection. Serum IGF-I was also determined 4 hours after the s.c. injections. RESULTS: During IGF-I treatment, four out of the six patients (two girls and two adults) developed progressive clinical symptoms and signs of hyperandrogenism (oligo/amenorrhoea and acne). Laboratory determinations showed a significant elevation in serum testosterone, delta 4-androstenedione and LH/FSH ratio. The hyperandrogenism occurred concomitantly with an increase in IGF-I serum and a decrease in serum insulin concentrations. Reduction in IGF-I dose or interruption in IGF-I treatment restored androgen levels to normal values. At the same time, the acne and oligomenorrhoea resolved. CONCLUSIONS: Overdosage of IGF-I can lead to androgenization, a previously undescribed undesirable effect of IGF-I. Long-term IGF-I treatment necessitates progressive adjustment of the IGF-I dose to avoid overtreatment.

Adolescent↗
PubMed1997

Increased number of IGF-I receptors on erythrocytes of women with polycystic ovarian syndrome.

OBJECTIVE: To test the hypothesis that insulin acts though ovarian IGF-I receptors to produce excessive amounts of androgens in polycystic ovarian syndrome (PCOS), by measuring the binding capacity of IGF-I receptors on erythrocytes and relating the findings to the degree of hyperandrogenism and hyperinsulinaemia. DESIGN: A case-control study of IGF-I receptors on erythrocytes of women with PCOS and age- and weight-matched controls. PATIENTS AND METHODS: IGF-I receptors on erythrocytes, serum levels of androgens, IGF-I, GH, basal insulin and insulin response during oral glucose tolerance test (oGTT) were measured after induced or spontaneous withdrawal bleeding in 10 women with PCOS and eight normo-ovulatory women. RESULTS: An increased number of IGF-I receptors was found on erythrocytes of patients with PCOS compared with the controls (P < 0.01), irrespective of their body mass index. Serum IGF-I levels were similar in both groups. The degree of hyperinsulinaemia, provoked by oGTT, correlated positively with basal insulin (r = 0.69; P = 0.003), but not with the number of IGF-I receptors. However, the number of IGF-I receptors correlated positively with androstenedione (r = 0.54, P = 0.0018). CONCLUSIONS: The findings in the present study that the number of IGF-I receptors and not the insulin levels correlate with serum androstenedione support the theory that the hyperandrogenism in PCOS is not a direct effect of the hyperinsulinaemia, but IGF-I mediated.

Adolescent↗
PubMed1997

Serum and renal IGF-I levels after uninephrectomy in the rat.

The hypertrophy of the remaining kidney following uninephrectomy (UNx) has been related to an increase in renal insulin growth factor-I (IGF-I) content. However, while the increase in renal IGF-I lasts for only days after UNx, renal hypertrophy continues for months. In the present study we investigated whether IGF-I also plays a role in the late post uninephrectomy growth of the remaining kidney. Renal IGF-I in the remnant kidney was greater than that of control kidneys (78.3 +/- 17.3 vs 56.0 +/- 14.0 pmol g-1; p < 0.05) 3 days after UNx, tended to remain higher 30 days after UNx (83.8 +/- 23.6 vs 57.3 +/- 14.5 pmol g-1; p = 0.07), but was similar to that of the control kidney when examined 60 days after UNx (66.6 +/- 15.6 vs. 70.4 +/- 6.7 pmol g-1). Serum IGF-I in uninephrectomized rats was similar to that of controls 3 days after UNx, started to increase above the control level at day 10 after UNx and remained higher 30 and 60 days after UNx (75.9 +/- 6.9 vs. 48.7 +/- 7.3 nmol l-1 at 30 days, and 81.2 +/- 13.7 vs 52.9 +/- 11.0 nmol l-1 at day 60, p < 0.05 for both). The kidney weight of uninephrectomized rats was higher by 21% than that of controls 3 days after UNx, by 45% 30 days after UNx and by 63% 60 days after UNx (p < 0.05 for all three observations). At the end of the study, the glomerular volume of uninephrectomized rats was higher by 36% than that of the controls (p < 0.05) We suggest that in the rat, while the initial post uninephrectomy hypertrophy of the remnant kidney is associated with and most probably mediated by an increase in renal IGF-I, the hypertrophy that persists in later post UNx periods is associated with and may be mediated by an increase in serum IGF-I.

Animals↗
PubMed1997

Lack of effect of methylphenidate on serum growth hormone (GH), GH-binding protein, and insulin-like growth factor I.

The aim of this study was to assess the growth hormone (GH) axis in methylphenidate (MPH)-treated and untreated boys with attention-deficit and hyperactivity disorder (ADHD), by evaluating serum GH, GH-binding protein (GHBP) activity, and insulin-like growth factor I (IGF-I) levels as compared to age-matched normal controls. Blood samples were taken from 42 boys (aged 6-16 years) diagnosed as having ADHD according to DSM-III-R criteria and confirmed by using the Schedule for Affective Disorder and Schizophrenia for school-age children (K[Kiddle]-SADS). A total of 21 patients were treated with MPH (5-20 mg/day; 0.15-0.77 mg/kg/day), on a drug holiday protocol, for 1-36 months, and 21 were drug naive. A total of 46 age-matched normal boys at height and weight within normal range served as controls. No significant differences were detected between the MPH-treated ADHD children, the untreated ADHD children, and the control children on fasting serum GH levels, GHBP activity, or IGF-I levels. Active treatment with MPH, in ADHD children on a drug holiday protocol, does not cause changes in GH axis as manifested by normal values of GH, GHBP, and IGF-I.

Adolescent↗
PubMed1997

Effect of different serum concentrations of growth hormone-binding protein (GHBP) on the regulation of GH receptor/GHBP gene transcription in a human hepatoma cell line.

Although high-affinity growth hormone (GH)-binding protein (GHBP) seems to mirror tissue GH receptor (GH-R) status and effects GH kinetics, the physiological importance and ultimate biological role of GHBP remain largely unknown and obscure. Therefore, the aims of this study were, first, to test the hypothesis that different serum concentrations of GHBP may regulate GH-R/GHBP gene transcription and, second, to define a new nonradioactive polymerase chain reaction (PCR) method to quantify GH-R/GHBP mRNA levels which was to compare with the RNase protection assay. Sera from patients with Laron-type dwarfism (n = 10) and adult obese patients (n = 7) containing distinct GH and GHBP concentrations were added to human hepatoma cells (HuH 7) cultured in a hormonally-adapted medium. GH-R/GHBP gene expression was studied 3 h after the addition of the sera. The results of the regulated GH-R/GHBP mRNA levels imply a direct impact of GHBP on GH-R/GHBP gene transcription under these circumstances. In conclusion, we set up a nonradioactive quantitative PCR method which enables the measurement and quantification of GH-R/GHBP mRNA. The results were identical with the data obtained using RNase protection assay. In addition, these results provide evidence that GHBP may have some effect on the regulation of the GH-R/GHBP transcription and that it is more than simply a shed or secreted product with extracellular destinations and functions. Our personal view, therefore, is that GHBP is rather an active player than an erratic extracellular domain of a receptor.

Adult↗
PubMed1997

Growth hormone increases and insulin-like growth factor-I decreases circulating lipoprotein(a)

BACKGROUND: Elevated serum lipoprotein(a) (Lp(a)) is a strong risk factor for coronary artery disease (CAD). Genetic factors appear to account for the major variance in Lp(a) levels but the contribution hormones make in modulating Lp(a) levels is not yet clear. In the present investigation we determined the effects of human growth hormone (hGH) and insulin-like growth factor-I (IGF-I) on circulating Lp(a). METHODS: Four groups of patients were studied. Group a: adults with GH deficiency (n = 7) treated with hGH (0.05 U/kg/day, s.c.); group b: girls with Turner syndrome (n = 7) treated with hGH (0.1 U/kg/day, s.c.); group c: prepubertal boys with idiopathic short stature (n = 6) treated with the GH secretagogue (GHRP) hexarelin (60 micrograms t.i.d. intranasally); group d: Laron syndrome patients (n = 10) treated with IGF-I (100-200 micrograms/kg/day, s.c.). Following overnight fasting, serum was sampled before the initiation of treatment and during 6-9 months treatment. RESULTS: Serum IGF-I rose significantly in all the subjects in all four groups. In the first three groups in which IGF-I was elevated by exogenous or endogenous GH stimulation, serum Lp(a) increased significantly (119 +/- 35%, P < 0.01; 126 +/- 44%, P < 0.05; 102 +/- 29%, P < 0.01 for groups a, b, and c respectively). By contrast, serum Lp(a) levels decreased in group d to whom exogenous IGF-I was administered (-66 +/- 5%, P < 0.001). The differential effect of endogenous vs exogenous IGF-I on serum Lp(a) paralleled the behaviour of serum insulin. Insulin was significantly increased in all the subjects receiving hGH or GHRP (65.2 +/- 31%, P = 0.109; 93.7 +/- 53%, P = 0.062; 353.8 +/- 52.7%, P < 0.01 for groups a, b, and c respectively) whereas insulin levels were reduced following exogenous administration of IGF-I (-34.1 +/- 9.1%, P < 0.01). CONCLUSIONS: We conclude that long-term GH treatment increases and IGF-I decreases circulating levels of Lp(a). These findings may have clinical relevance in view of the increasing use of hGH in children and adults and the role of Lp(a) as a CAD risk factor.

Adult↗
PubMed1997

Long-term effects of insulin-like growth factor (IGF)-I on serum IGF-I, IGF-binding protein-3 and acid labile subunit in Laron syndrome patients with normal growth hormone binding protein.

A minority of patients with Laron syndrome have normal serum GH binding protein (GHBP), indicating that the defect is elsewhere than in the extracellular domain of the GH receptor. We have evaluated the effect of long-term IGF-I treatment on serum IGF-binding protein (IGFBP)-3 and the acid-labile subunit (ALS) in three sibling with Laron syndrome caused by a GH post-receptor defect and with normal GHBP. The children (a boy aged 3 years, a girl aged 4 years and a boy aged 10 years) were treated by daily s.c. injection of IGF-I in a dose of 150 micrograms/kg. IGFBP-3 was measured by RIA and Western ligand blotting, ALS by RIA. Based values of IGFBP-3 and ALS were low. During IGF-I treatment, the IGFBP-3 concentrations in the girl gradually increased, whereas in the boys there was a 60% decrease during the first week, followed by gradual increase towards baseline. The ALS concentrations followed a similar pattern. We conclude that IGF-I treatment induces and initial suppression and then an increase in the IGFBP-3 and ALS concentrations, confirming data from animal experiments that IGFBP-3 synthesis is not solely under GH control. The differences in responsiveness between the female and male siblings may reflect genetic differences, or lower circulating concentrations of IGF-I in the boys compared with the girl.

Carrier Proteins↗
PubMed1996

Differential effect of insulin-like growth factor-1 and growth hormone on hypothalamic regulation of growth hormone secretion in the rat.

Pharmacological administration of either growth hormone (GH) or insulin-like growth factor 1 (IGF-1) were reported to inhibit endogenous GH release in humans and in the laboratory animal. We have evaluated the short-term differential mechanisms whereby the two hormones affect hypothalamic regulation of GH secretion. Wistar male rats (90 days old) were injected i.p. with either GH (recombinant GH NIAMDD, Baltimore, MD, USA), rIGF-1 (Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan) or saline. Animals were sacrificed at 15, 30, 60 and 120 minutes following injection. Hypothalami were dissected and extracted immediately and the levels of growth hormone-releasing hormone (GHRH) and somatostatin were determined using specific antisera. Trunk blood was collected for GH and IGF-1 determination by RIA. Administration of IGF-1 or GH markedly decreased hypothalamic somatostatin stores by 77% and 54% respectively, within 15 minutes. Concomitantly, the wide range of GH levels found in the control group was reduced in the IGF-1 treated group suggesting that the pulsatile pattern of GH secretion was suppressed. Growth hormone administration induced an increase in hypothalamic GHRH stores (60% at 120 minutes). During this period serum IGF-1 levels were not altered. It is suggested that short term modulation of hypothalamic neurohormones by GH and IGF-1 is mediated by rapid stimulation of somatostatin release by both hormones, and inhibition of GHRH release is induced only by GH.

Analysis of Variance↗
PubMed1996

Insulin-like growth factor-I decreases serum lipoprotein (a) during long-term treatment of patients with Laron syndrome.

An increased circulating level of lipoprotein(a) [Lp(a)] is a well-recognized risk factor for coronary artery disease. While much remains to be understood about its regulation and physiological functions, we explored the effect of recombinant insulin-like growth factor-I (IGF-I) administration on circulating Lp(a) levels in 10 Laron syndrome (LS) patients (five children and five adults) with inherited IGF-I deficiency. There was no relationship between pretreatment or posttreatment Lp(a) levels and age and sex of the patients. With IGF-I treatment for 6 to 12 months, there was a significant reduction in Lp(a) (65.7% +/- 15.5%, P < .0001) from the pretreatment level of 76 +/- 45 mg/L to the posttreatment level of 29 +/- 26 mg/L. This decrease was dosage-dependent on the IGF-I administered (r = .685, F = 0.708, P = .029) and correlated more strongly with the dosage ratio of the end to the beginning of treatment (r = .78, F = 12.23, P = .008). The higher the IGF-I dose and the higher the dose ratio, the greater the Lp(a) decrease and the lower the Lp(a) at the end of treatment. In conclusion, we observed a dose-dependent relationship between IGF-I administration and Lp(a) reduction in patients with LS. Further studies are needed to elucidate the mechanism of the effect, but our findings suggest a possible metabolic link between these two and shed more light on the regulation of apolipoprotein(a) [apo(a)] expression. It could also open an avenue for additional therapeutic usage of IGF-I.

Adolescent↗
PubMed1996

Insulin-like growth factor-I raises serum procollagen levels in children and adults with Laron syndrome.

OBJECTIVE: Recombinant IGF-I is now available for the treatment of GH insensitivity (Laron syndrome). We have determined the effects of IGF-I on soft connective tissue and bone metabolism in a group of patients with this disorder. PATIENTS AND DESIGN: Thirteen patients with Laron syndrome (LS) (8 children and 5 adults) were included in the study. The children with LS were treated with IGF-I for 3 years with daily doses of 150-200 micrograms/kg. The adult LS patients were treated for 9 months with daily doses of 50-120 micrograms/kg. Blood samples for procollagens were collected before, during and at the end of IGF-I treatment. MEASUREMENTS: Serum levels of the carboxyterminal propeptide of type I procollagen (PICP), the aminoterminal propeptide of type III procollagen (PIIINP) and of the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were determined before and during IGF-I administration. RESULTS: Untreated patients with LS had lower than normal serum levels of PICP and PIIINP for age. IGF-I treatment increased significantly the PIIINP levels in children from 7.2 +/- 2.8 (SD) to 12.5 +/- 2.2 micrograms/l (P < 0.001), and in adults from 2.7 +/- 1.0 to 8.4 +/- 3.6 micrograms/l (P < 0.001); serum PICP increased from 243 +/- 123 to 384 +/- 190 micrograms/l (P < 0.087) in children, and in adults from 43.4 +/- 8.1 to 135.8 +/- 41.9 micrograms/l (P < 0.001). ICTP levels in children increased from 9.7 +/- 3.7 to 14.3 +/- 5.9 micrograms/l (P < 0.001) and in adult patients levels increased from 3.6 +/- 0.9 to 5.5 +/- 2.2 micrograms/l (P < 0.001) during treatment and returned to basal values after stopping IGF-I administration. CONCLUSIONS: Low procollagen levels in untreated Laron syndrome patients and their rise during replacement therapy with IGF-I provide evidence that IGF-I plays an important role in bone and soft connective tissue metabolism and that serum procollagen may serve as a marker to reflect some of the biochemical changes induced by IGF-I in connective tissue in the initial periods of treatment.

Adolescent↗
PubMed1996

Desensitization from long-term intranasal treatment with hexarelin does not interfere with the biological effects of this growth hormone-releasing peptide in short children.

A clinical, prospective experiment was carried out to determine whether long-term intranasal administration of the growth hormone-releasing peptide hexarelin (His-D-2-methyl-Trp-Ala-Trp-D-Phe -Lys-NH2) affects pituitary growth hormone secretion. Hexarelin (60 micrograms/kg t.i.d.) was administered to seven prepubertal constitutionally short children (mean age +/- SD = 7.6 +/- 2.4 years). Serum human growth hormone (hGH) response to an intranasal (20 micrograms/kg) and i.v. (1 mircogram/kg) bolus of hexarelin before, during and after 6-10 months of treatment was measured. The mean ( +/- SD) peak rise of hGH to the intranasal bolus before treatment was 70.6 +/- 28.2 mU/l. After 7 days of hexarelin treatment, mean peak values dropped to 34.1 +/- 15.7 mU/l (p < 0.002) and thereafter remained constant for 6 months of treatment at 37.5 +/- 10.3 mU/l (p < 0.03). The pretreatment peak to th i.v. hexarelin bolus was 84.8 +/- 52.5 mU/l, and at the end of the treatment period it was 19.8 +/- 10.9 mU/l (p < 0.05). Three months after stopping treatment the mean ( +/- SD) hGH response rose to 42.1 +/- 4.7 mU/l (p < 0.005). Growth velocity increased from 5.3 +/- 0.9 cm/year (before treatment) to 7.4 +/- 1.6 cm/year at 6-10 months of treatment (p < 0.005). In conclusion, teh partial suppression of pituitary hGH responsiveness to long-term intranasal hexarelin treatment, probably due to desensitization, does not affect the observed increase in growth velocity.

Administration, Intranasal↗
PubMed1995

Intranasal administration of the GHRP hexarelin accelerates growth in short children.

OBJECTIVE: Hexarelin is a recently synthesized small growth hormone releasing peptide (GHRP) (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys- NH2). It is active by intravenous, oral and intranasal administration in animals and man. The aim of this study was to find out whether long-term administration of this peptide would promote growth in short children. DESIGN AND PATIENTS: Intranasal hexarelin was administered in a dose of 60 micrograms/kg thrice daily to 8 prepubertal short children aged 4-11.6 years for periods of up to 8 months. RESULTS: Hexarelin treatment stimulated insulin-like growth factor-I (IGF-I) secretion raising the level from 10.4 +/- 3.9 (SD) to 14.1 +/- 4.6 nmol/l (P < 0.004). The rise in IGF-I led to a significant increase in the mean (+/- SD) linear growth velocity from 5.3 +/- 0.8 to 8.3 +/- 1.7 cm/year (P < 0.0001). There was also a significant decrease in skinfold thickness despite increase in body weight and an increase in head circumference. Additional findings were a rise in serum phosphate from 1.5 +/- 0.1 to 1.8 +/- 0.1 mmol/l (P < 0.004) and of alkaline phosphatase from 219 +/- 74 to 261 +/- 75 U/l (P < 0.05). CONCLUSIONS: The long-term GH/IGF-I stimulating, anabolic and growth promoting effects achieved by intranasal administration of this hexapeptide, seemingly without undesirable side-effects, suggests clinical potential for this new class of drugs.

Administration, Intranasal↗
PubMed1994

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 metabolism, we compared SHBG levels in patients treated with IGF-I and GH. DESIGN AND PATIENTS: Serum levels of IGF-I, insulin and SHBG were measured before and during the treatment of patients with IGF-I or GH. Blood samples were drawn in the fasting state, prior to and during therapy, 24 hours after drug administration. Sixteen children and adults with Laron syndrome (LS) received daily s.c. injections of IGF-I (120-150 micrograms/kg) for up to 5 months. Three adults with isolated GH deficiency (IGHD) received daily s.c. injections of GH (0.03-0.06 U/kg) for 16 months. Two groups of nine prepubertal children with constitutional short stature (CSS) received GH (0.1 U/kg/day) for 3 months. MEASUREMENTS: Serum levels of insulin and acid extractable IGF-I were determined by RIA, and that of SHBG by IRMA. RESULTS: Basal insulin and SHBG levels were within normal range in the LS, IGHD and CSS patients. IGF-I levels were low in LS and IGHD patients, and normal in the CSS children. The mean peak response to chronic therapy was as follows: in LS patients, IGF-I administration decreased insulin levels to 62%, and increased SHBG levels by 64% above basal values. Chronic GH therapy in IGHD caused a marked rise in both IGF-I levels (473%), and insulin levels (96%), and a gradual decline of SHBG to 75% of the basal concentration. In GH treated CSS patients, serum IGF-I peaked at 80% and insulin levels at 102% above the respective basal levels, while SHBG decreased to 83% after 5 days of treatment. CONCLUSION: The results obtained in Laron syndrome, isolated GH deficiency and constitutional short stature patients treated with IGF-I or GH, indicate that serum insulin had consistently an inverse relation with the levels of circulating SHBG. No relation was found between IGF-I and SHBG levels.

Adult↗
PubMed1994

Serum growth hormone-binding protein (GHBP) activity is decreased by administration of insulin-like growth factor I in three Laron syndrome siblings with normal GHBP.

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.

Carrier Proteins↗
PubMed1994

GH and GHBP activity and not IGF-1 and its receptor activity express growth velocity reduction during treatment of central precocious puberty by a superactive GNRH analogue.

We studied six patients with central precocious puberty (CPP) (five girls and one boy, aged 9-14.4 years) before and after 5 and 12 months of treatment with GnRH-A (D-TRP-6-LHRH-depo, DECAPEPTYL Ferring, Sweden), and 14 age-matched prepubertal children serving as controls. GnRH suppressed gonadal sex hormone secretion and arrested the gonadarche development. Growth velocity decreased from 9.8 +/- 1.6 (mean +/- SD) to 4.6 +/- 1.0 cm/year after 1 year of treatment. Basal serum IGF-1 levels of the CPP patients were 35.4 +/- 2.8 nmol/l, which was significantly higher than that of the controls (18.8 +/- 1.9, P = 0.00007). After GnRH-A there was a slight but significant increase in serum IGF-1 levels from 35.4 +/- 2.8 (mean +/- SE) to 40.3 +/- 2.1 nmol/l after 5 months (mean difference of 4.9 +/- 1.7, P = 0.02), reversing to 35.6 +/- 2.8 nmol/l after 12 months. The number of high affinity IGF-1 binding sites on erythrocytes (RBC) in the controls was 3.3 +/- 0.3 sites/cell, similar to that found in the patients before treatment. Following therapy, the number of the binding sites decreased from 4.0 +/- 0.8 (mean +/- SE) to 2.5 +/- 0.6 sites/cell after 5 months (mean difference of -1.4 +/- 0.5, P = 0.01), to 2.7 +/- 0.7 sites/cell after 12 months. Basal levels of plasma GH in the CPP patients were 7.1 +/- 1.3 ng/ml, significantly higher than those of the controls (1.2 +/- 0.2, P = 0.00001). Treatment decreased plasma GH in patients from 7.1 +/- 1.3 to 1.3 +/- 0.3 ng/ml after 5 months (mean difference of -5.8 +/- 1.3, P = 0.003) and to 2.7 +/- 1.5 ng/ml after 12 months. The GH binding protein (GHBP) activity in the controls was 76.2 +/- 6.2% relative specific binding, similar to that of the patients before therapy. The mean basal GHBP activity of the patients increased from 75.5 +/- 7.3 to 101 +/- 6.4% (mean difference of 25.5 +/- 9.7, P = 0.01) after 5 months and to 90.1 +/- 5.6% after 12 months of treatment. In conclusion, plasma GH and its receptor activity are a better indicator of the GnRH-A effect on growth than IGF-1 and its receptor activity.

Adolescent↗
PubMed1993

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.

Adolescent↗