DIAGNOSTIC VALUE OF SERUM INSULIN- LIKE GROWTH FACTOR BINDING PROTEIN- 3 IN CHILDREN WITH OR WITHOUT GROWTH HORMONE DEFICIENCY

OBJECTIVE: To study the value of serum insulin-like growth factor binding protein-3 (IGFBP-3) levels in differential diagnosis of growth hormone deficiency (GHD). METHODS: To measure serum IGFBP-3 levels by RIA in normal children and adolescents, GHD children and short-stature children without GHD. RESULTS: Serum level of IGFBP-3 in 129 children with untreated GHD and with no pubertal development was 1.6 +/- 0.9 mg/L, which was less than that in normal group of the same age, but overlapped with the normal children in Tanner stage I. After six-month treatment with recombinant human growth hormone (rhGH), serum level of IGFBP-3 in 59 GHD significantly increased from 1.3 +/- 0.7 mg/L to 2.7 +/- 0.9 mg/L, accompanied by an increase of body heights, growth velocities and serum level of IGF-1. Serum level of IGFBP-3 in 55 short-stature children without GHD was 3.3 +/- 2.2 mg/L, which was not significantly different from that in normal group. CONCLUSION: Serum IGFBP-3 level can reflect the status of GH secretion in children with GHD and is a useful marker for differential diagnosis of GHD.

Insulin-like Growth Factor-Ⅰ Gene Cloning and Protein Expression in Bovine Trabecular Meshwork Tissue and Cells

Whether cultured bovine trabecular meshwork cells and trabecular tissue ex vivo express insulin like growth factor I (IGF Ⅰ) messenger RNA (mRNA) and protein was investigated. Total RNA of cultured bovine trabecular meshwork cells as well as trabecular meshwork tissue freshly excised from bovine eyes was extracted, and reverse transcriptase polymerase chain reaction (RT PCR) was used to detect IGF Ⅰ mRNA. RT PCR product was verified by sequencing. Immunohistochemical stain was used to detect IGF Ⅰ protein. The results showed that a single PCR amplified product was obtained, and the sequence was homologous to the known sequence.. IGF Ⅰ immunostain was positive in the cytoplasm of trabecular meshwork cells. It was concluded that trabecular meshwork cells produce IGF Ⅰ and contribute to the presence of IGF Ⅰ in trabecular meshwork microenvironment as well as aqueous humor. Trabecular meshwork cells were affected by IGF Ⅰ not only through paracrine, but also autocrine action. Whether abnormal down regulations in IGF Ⅰ production may contribute to the pathogenesis of primary open angle glaucoma and the possibility of promoting the autocrine action of IGF Ⅰ by trabecular meshwork cells to treat the diesease is worth further investigation.

On implications of somatostatin in diabetic retinopathy

Somatostatin,a naturally produced neuroprotective peptide,depresses excitatory neurotransmission and exerts anti-proliferative and anti-inflammatory effects on the retina.In this review,we summarize the progress of somatostatin treatment of diabetic retinopathy through analysis of relevant studies published from February 2019 to February 2023 extracted from the PubMed and Google Scholar databases.Insufficient neuroprotection,which occurs as a consequence of declined expression or dysregulation of retinal somatostatin in the very early stages of diabetic retinopathy,triggers retinal neurovascular unit impairment and microvascular damage.Somatostatin replacement is a promising treatment for retinal neurodegeneration in diabetic retinopathy.Numerous pre-clinical and clinical trials of somatostatin analog treatment for early diabetic retinopathy have been initiated.In one such trial(EUROCONDOR),topical administration of somatostatin was found to exert neuroprotective effects in patients with pre-existing retinal neurodysfunction,but had no impact on the onset of diabetic retinopathy.Overall,we concluded that somatostatin restoration may be especially beneficial for the growing population of patients with early-stage retinopathy.In order to achieve early prevention of diabetic retinopathy initiation,and thereby salvage visual function before the appearance of moderate non-proliferative diabetic retinopathy,several issues need to be addressed.These include the needs to:a)update and standardize the retinal screening scheme to incorporate the detection of early neurodegeneration,b)identify patient subgroups who would benefit from somatostatin analog supplementation,c)elucidate the interactions of somatostatin,particularly exogenously-delivered somatostatin analogs,with other retinal peptides in the context of hyperglycemia,and d)design safe,feasible,low cost,and effective administration routes.

Effect of growth hormone on small intestinal homeostasis relation to cellular mediators IGF-I and IGFBP-3

AIM:To evaluate the effects of growth hormone(GH) on the histology of small intestines which might be related to the role of insulin like growth factor(IGF)-I, IGF-binding protein 3(IGFBP-3)and its receptors. METHODS:Twelve week-old adult male Wistar albino rats were divided into two groups.The study group(n =10),received recombinant human growth hormone (rGH)at a dose of 2 mg/kg per day subcutaneously for 14 d and the control group(n=10)received physiologic serum.Paraffin sections of jejunum were stained with periodic acid shift(PAS)and hematoxylin and eosin(HE) for light microscopy.They were also examined for IGF-I, IGFBP-3 and IGF-receptor immunoreactivities.Staining intensity was graded semi-quantitatively using the HS- CORE. RESULTS:Goblet cells and the cells in crypt epitheliawere significantly increased in the study group compared to that of the control group.We have demonstrated an increase of IGF-I and IGFBP-3 immunoreactivities in surface epithelium of the small intestine by GH application.IGF-I receptor immunoreactivities of crypt,villous columnar cells,enteroendocrine cells and muscularis mucosae were also more strongly positive in the study group compared to those of in the control group. CONCLUSION:These findings confirm the important trophic and protective role of GH in the homeostasis of the small intestine.The trophic effect is mediated by an increase in IGF-I synthesis in the small intestine, but the protective effect is not related to IGF-I.

Research on construction and identification of lentiviral vector of expressing miRNA targeting IGF1R gene regulated by survivin promoter and its inhibition to liver cancer cell growth

Objective： The aim of the study was to investigate the interference and anti-tumor effects of lentiviral vector of miRNA targeting IGF1R gene regulated by survivin promoter. Methods： The fragment of the survivin promoter was acquired by PCR amplification and inserted into pPRIME to recombinant plasmid sur-pPRIME. The complementary DNA containing both sense and antisense Oligo DNA of the targeting sequence was designed, synthesized and cloned into the sur-pPRIME vector, named sur-pPRIME-IGF1R-miR30-shRNA. Viruses were propagated on 293T cells. Viruses were purified by CsCI gradient according to standard techniques, and functional PFU titers were determined by plaque assay on 293 cells. The effect of sur-pPRIME-IGF1R-miR30-shRNA on IGF1R expression of Hep3B cells was detected by RT-PCR and Western blot. The antitumor potential of sur-pPRIME-IGF1R-miR30-shRNA to Hep3B cells was evaluated by CCK-8 assay. Results： sur-pPRIME-IGF1R-miR30-shRNA was constructed successfully. Functional PFU titers of sur-pPRIME-IGF1R-miR30-shRNA were 4.58×10^9 PFU/rnL. Sur-pPRIME-IGF1R-miR30-shRNA was more effective to inhibit IGF1R expression in mRNA or protein levels and the proliferation of Hep3B cells. Conclusion： sur-pPRIME-IGF1R-miR30-shRNA expressing IGF1R-siRNA can inhibit IGF1R expression and may be used for further investigation of gene therapy of liver cancer.

Effect of glucocorticoid treatment on insulin like growth factor-Ⅰ and its binding proteins in children with nephrotic syndrome

Objective To identify the changes in serum insulin like growth factor Ⅰ (IGF Ⅰ) and IGF binding proteins (IGFBPs) in children with nephrotic syndrome (NS) and the effect of glucocorticoid on serum IGF Ⅰ and IGFBPs Methods We measured serum IGF Ⅰ and IGFBPs levels by radioimmune assay and immune radiomagnetic assay in 36 children with NS, consisting of an active stage group (ANS, n=12), a remission stage group (RE, n=12), an active stage group with glucocorticoid treatment (GNS, n=12), and a normal control group (NC, n=10) Results 1) Compared to NC, serum levels of IGF Ⅰ and IGFBP 3 were decreased ( P <0 01); serum levels of IGFBP 1 and IGFBP 2 were increased ( P <0 01) in the ANS group 2) Serum levels of IGF Ⅰ and IGFBP 3 were higher and IGFBP 1 and IGFBP 2 were lower in the RE Group than in theANS Group ( P <0 01) 3) Compared to the ANS group, serum levels of IGF Ⅰ and IGFBP 3 were increased ( P <0 01) and serum levels of IGFBP 1 and IGFBP 2 were decreased ( P <0 01) in the GNS group 4) A correlation was found between serum levels of IGFBP 3 and albumin in the active stage group ( r =0 76, P <0 01) There was also a correlation between serum levels of IGF Ⅰ and IGFBP 3 and an inverse correlation between the serum level of IGF Ⅰ and serum levels of IGFBP 1 and IGFBP 2 in the ANS group No other correlations were observed Conclusions The serum levels of IGF Ⅰ and IGFBPs are altered in children in the active stage of NS, but return to normal in the remission stage GC treatment may influence serum IGF Ⅰ and IGFBPs in children with NS Changes in IGF Ⅰ and IGFBPs levels may play a role in the growth retardation of NS children

Influence of growth hormone-insulin-like growth factor Ⅰ axis on normal pregnancy

Objective To investigate the role of growth hormone-insulin-like growth factor Ⅰ (IGF-Ⅰ) axis in normal pregnancy.Methods Totally, 116 normal pregnant women were recruited from January 1997 to June 1998, with 20 normal nonpregnant women as controls. Maternal growth hormone (GH) and IGF-Ⅰ concentrations were assayed by RIA and enzyme-linked immunosorbent assay, respectively.Results Maternal serum levels of GH increased throughout gestation, reached a peak at 25 weeks of pregnancy and remained fairly high (χ2=40.458, P<0.0001). There was a significant difference between samples at 5-9 week gestational age and the controls (3.45?μg/L vs 1.61?μg/L, P<0.05). The maternal serum levels of IGF-Ⅰ increased rapidly throughout gestation from 29-week gestation and reached a peak of 188.86?μg/L at term delivery (χ2=50.224, P<0.0001).Conclusions Maternal GH levels increased progressively throughout gestation, which correlated with fetal growth. Maternal GH may regulate nutrition supply among mother, placenta and the fetus and play an important role in transporting nutritional substrates by the placenta. The maternal IGF-Ⅰ in the third trimester may promote fetal growth and placental functions.

Retinoic acid regulated insulin-like growth factor gene expression in cord blood lymphocytes

Objective To explore the immune promotion mechanism of retinoic acid (RA).Methods Reverse Transcription-Polymerase chain reaction (RT-PCR) was used to detect the gene expression of insulin like growth factor Ⅰ (IGF-Ⅰ) and IGF receptors (IGF-IR and IGF-IIR) in vitro, and their regulation by RA in human cord blood lymphocyte (CBL). Results Significant upregulation of IGF-I, IGF-IR and IGF-IIR mRNA was found at 6-24 hours in CBL incubated with physiologic concentrations of RA as compared to those without RA. Conclusion The enhancement of IGF expression may be an important pathway for vitamin A to promote immune cellular functions.

The change of insulin-like growth factor-1 in diabetic patients with neuropathy

Objective To evaluate the possible relationship between insulin like growth factor 1 (IGF 1) and diabetic neuropathy (DNP). Methods Sixty nine patients with Type 2 non insulin dependent diabetes (54 with peripheral neuropathy and 15 without neuropathy) were observed. Normal controls were 34 non diabetic persons. Diabetic peripheral neuropathy diagnosis was carried out taking into account results of NS, ND, NC and AF. After an overnight fast, blood was taken for IGF 1, glucose, hemoglobin Alc, C peptide, and insulin. Plasma IGF 1 was measured by radioimmunoassay (RIA) method. Results The neuropathic group had significantly lower levels for IGF 1 (86.43 ng/ml ±45.18 ng/ml) compared to normal controls (119.68 ng/ml ±89.42 ng/ml) (P<0.05), and to diabetic patients without neuropathy (113.75 ng/ml ±66.58 ng/ml) (P< 0.05). No significant difference was found between diabetic non neuropathic group and normal control subjects (P>0.05). In diabetic subjects there was a positive correlation (γ=0.27, P<0.05) between IGF 1 and beat to variation in heart rate. There were negative correlation bwteen IGF 1 and postprandial blood glucose (γ=-0.3, P< 0.05), and aspartic acid translocase (γ=-0.27, P<0.05). Conclusion In diabetic patients with peripheral neuropathy there are abnormalities of IGF 1 that may contribute to the pathogeneses of diabetic neuropathy.

Androgenic regulation of novel genes in the epididymis

The epididymis is critically dependent on the presence of the testis. Although several hormones, such as retinoids and progestins, and factors secreted directly into the epididymal lumen, such as androgen binding protein and fibroblast growth factor, might play regulatory roles in epididymal function, testosterone （T） and its metabolites, dihydrotestosterone （DHT） and estradiol （E2）, are accepted as the primary regulators of epididymal structure and functions, with the former playing the greater role. To ascertain the molecular action of androgens on the epididymis, three complementary approaches were pursued to monitor changes in gene expression in response to different hormonal milieux. The first was to establish changes in gene expression along the epididymis as androgenic support is withdrawn. The second was to determine the sequence of responses that occur in an androgen deprived tissue upon re-administration of the two metabolites of T, DHT and E2. The third was to study the effects of androgen withdrawal and re-administration on gene expression in immortalized murine caput epididymidal principal cells. Specific responses were observed under each of these conditions, with an expected major difference in the panoply of genes expressed upon hormone withdrawal and re-administration; however, some key common features were the common roles of genes in insulin like growth factor/epidermal growth factor and the relatively minor and specific effects of E2 as compared to DHT. Together, these results provide novel insights into the mechanisms of androgen regulation in epididymal principal cells. （Asian J Androl 2007 July; 9： 545-553）