scholarly journals Pharmacogenomics of insulin-like growth factor-I generation during GH treatment in children with GH deficiency or Turner syndrome

2013 ◽  
Vol 14 (1) ◽  
pp. 54-62 ◽  
Author(s):  
A Stevens ◽  
◽  
P Clayton ◽  
L Tatò ◽  
H W Yoo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Turner Syndrome ◽  
Gh Deficiency ◽  
Insulin Like Growth Factor ◽  
Gh Treatment ◽  
Factor I ◽  
Growth Factor I

Endotoxin attenuates growth hormone-induced hepatic insulin-like growth factor I expression by inhibiting JAK2/STAT5 signal transduction and STAT5b DNA binding

2007 ◽  
Vol 292 (6) ◽  
pp. E1856-E1862 ◽  
Author(s):  
Yu Chen ◽  
Difei Sun ◽  
Vidya M. R. Krishnamurthy ◽  
Ralph Rabkin
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Janus Kinase ◽  
Cytokine Gene Expression ◽  
Cytokine Signaling ◽  
Insulin Like Growth Factor ◽  
Gh Treatment ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Gram-negative sepsis with release of endotoxin is a frequent cause of cachexia that develops partly because of resistance to growth hormone (GH) with reduced insulin-like growth factor-I (IGF-I) expression. We set out to more fully characterize the mechanisms for the resistance and to determine whether in addition to a defect in the janus kinase 2 (JAK2)-signal transducer and activator of transcription (STAT) 5b pathway, required for GH-induced IGF-I expression, there might also be a more distal defect. Conscious rats were given endotoxin and studied 4 h later. In liver of these animals, GH-induced JAK2 and STAT5 phosphorylation was impaired and appeared to be caused, at least in part, by a marked increase in hepatic tumor necrosis factor-α and interleukin-6 mRNA expression accompanied by elevated levels of inhibitors of GH signaling, namely cytokine-inducible suppressors of cytokine signaling-1 and -3 and cytokine-inducible SH2 protein (CIS). Nuclear phosphorylated STAT5b levels were significantly depressed to 61% of the control values and represent a potential cause of the reduced GH-induced IGF-I expression. In addition, binding of phosphorylated STAT5b to DNA was reduced to an even greater extent and averaged 17% of the normal control value. This provides a further explanation for the impaired IGF-I gene transcription. Interestingly, when endotoxin-treated rats were treated with GH, there was a marked increase in proinflammatory cytokine gene expression in the liver. If such a response were to occur in humans, this might provide a partial explanation for the adverse effect of GH treatment reported in critically ill patients.

scholarly journals Effects of Short-Term Insulin-Like Growth Factor-I (IGF-I) or Growth Hormone (GH) Treatment on Bone Metabolism and on Production of 1,25-Dihydroxycholecalciferol in GH-Deficient Adults1

1998 ◽  
Vol 83 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Tarcisio Bianda ◽  
Yvonne Glatz ◽  
Roger Bouillon ◽  
Ernst Rudolf Froesch ◽  
Christoph Schmid
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Bone Formation ◽  
Bone Turnover ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Gh Treatment ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Administration of insulin-like growth factor-I (IGF-I) or growth hormone (GH) is known to stimulate bone turnover and kidney function. To investigate the effects of IGF-I and GH on markers of bone turnover, eight adult GH-deficient patients (48 ± 14 yr of age) were treated with IGF-I (5 μg/kg/h in a continuous sc infusion) and GH (0.03 IU/kg/daily sc injection at 2000 h) in a randomized cross-over study. We monitored baseline values for three consecutive days before initiating the five-day treatment period, as well as the wash-out period of ten weeks. Serum osteocalcin, carboxyterminal and aminoterminal propeptide of type I procollagen (PICP and PINP, respectively) increased significantly within 2–3 days of both treatments (P < 0.02) and returned to baseline levels within one week after the treatment end. The changes in resorption markers were less marked as compared with formation markers. Total 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) rose significantly, whereas PTH and calcium levels remained unchanged during either treatment. Conclusions: Because the rapid increase in markers of bone formation was not preceded by an increase in resorption markers, IGF-I is likely to stimulate bone formation by a direct effect on osteoblasts. Moreover, because PTH, calcium, and phosphate remained unchanged, IGF-I appears to stimulate renal 1α-hydroxylase activity in vivo.

Effect of growth hormone treatment on the distribution of insulin-like growth factor-I between plasma and lymph of lactating sheep

1992 ◽  
Vol 132 (3) ◽  
pp. 339-344 ◽  
Author(s):  
S. R. Davis ◽  
S. C. Hodgkinson ◽  
C. G. Prosser ◽  
P. D. Gluckman ◽  
F. C. Buonomo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Molecular Mass ◽  
Binding Proteins ◽  
Size Exclusion ◽  
Insulin Like Growth Factor ◽  
Gh Treatment ◽  
Factor I ◽  
Total Binding ◽  
Igf I ◽  
Growth Factor I

ABSTRACT Plasma and mammary efferent lymph concentrations of insulin-like growth factor I (IGF-I) were determined in lactating ewes before and after treatment with GH (10 mg/day) for 3 days. The lymph:plasma ratio of IGF-I increased from 0·34 to 0·47 after GH treatment when the IGF-I content of plasma increased by 19·4 nmol/l (from 32·1 nmol/l) and lymph by 13·7 nmol/l (from 10·7 nmol/l). This increase in the relative content of IGF-I in lymph was associated with increased lymph content of IGF-I in a lower molecular mass pool (nominally 50 kDa) derived by size exclusion chromatography. GH treatment increased the total binding capacity for IGF-I in both high (150 kDa) and low (50 kDa) molecular mass pools of plasma and the 150 kDa pool in lymph but there was a proportionally greater increase in 50 kDa total binding in lymph relative to plasma. Further, GH treatment increased the 'saturation' of the 50 kDa binding proteins but decreased the 'saturation' of the 150 kDa fraction, in both plasma and lymph. Ligand blot analysis of IGF-binding proteins (IGFBPs) in plasma and lymph showed that GH treatment of lactating sheep increased IGFBP-3 and decreased IGFBP-2 in plasma and lymph. Radioimmunoassay of IGFBP-2 showed that while GH treatment reduced the plasma content of IGFBP-2 by about half, the lymph:plasma ratio was increased from 0·68 to 0·87. GH treatment of lactating ewes not only increased the IGF-I content of plasma but increased the apparent efficiency of transfer of IGF-I across capillary endothelium to mammary efferent lymph. Journal of Endocrinology (1992) 132, 339–344

Plasma free insulin-like growth factor I concentrations in growth hormone deficiency in children and adolescents

1996 ◽  
Vol 134 (2) ◽  
pp. 184-189 ◽  
Author(s):  
Yukihiro Hasegawa ◽  
Tomonobu Hasegawa ◽  
Makoto Takada ◽  
Yutaka Tsuchiya
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Gh Deficiency ◽  
Hormone Deficiency ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Factor I ◽  
Igf I ◽  
Igf Binding ◽  
Growth Factor I

Hasegawa Y, Hasegawa T, Takada M, Tsuchiya Y. Plasma free insulin-like growth factor I concentrations in growth hormone deficiency in children and adolescents. Eur J Endocrinol 1996;134:184–9. ISSN 0804–4643. Serum levels of total insulin-like growth factor I (IGF-I) correlate with growth hormone (GH) secretory status and are a useful parameter in the diagnostic evaluation of GH deficiency. Serum total IGF-I levels represent the combined quantity of free or unbound IGF-I and IGF-I that is bound to specific IGF binding proteins. Free IGF-I (fIGF-I), which is postulated to be the bioactive fraction, accounts for only a small fraction of the total amount. We have recently developed a new immunoradiometric assay (IRMA) for plasma fIGF-I and have investigated fIGF-I in relation to GH status. The simple, non-extraction assay procedure involves the capture of unbound IGF-I by anti-IGF-I antibody coated to polystyrene beads and detection by a radiolabelled anti-IGF-I antibody directed to a separate epitope. Preliminary studies demonstrated that the f IGF-I IRMA does not measure IGF-I that is complexed to IGF-binding proteins and that the equilibrium between the free and bound fractions is not disturbed during the assay. Free IGF-I levels were compared to total IGF-I levels measured in the same IRMA after acid–ethanol extraction of the samples. Normal levels of fIGF-I from infancy through adulthood were found to have a close correlation with total IGF-I levels, with the lowest levels occurring in infancy and peak levels during puberty. Patients with complete GH deficiency had low levels of both fIGF-I and total IGF-I, with 94% and 100% of the levels below the 5th percentile for age, respectively. On the other hand, approximately 90% of patients with normal IGF binding protein-3 levels among partial GH deficiency and normal short children had free and total IGF-I levels above the 5th percentile for age. These data indicate that the clinical utility of plasma fIGF-I measurements is similar to measurements of total IGF-I in the evaluation of childhood GH deficiency. Yukihiro Hasegawa, Division of Endocrinology and Metabolism, Tokyo Metropolitan Kiyose Children's Hospital, 1-3-1 Urnezono Kiyose, Tokyo 204, Japan

Regulation of plasma and tissue levels of insulin-like growth factor-I by nutrition and treatment with growth hormone in sheep

1993 ◽  
Vol 136 (2) ◽  
pp. 217-224 ◽  
Author(s):  
K. M. Hua ◽  
R. Ord ◽  
S. Kirk ◽  
Q. J. Li ◽  
S. C. Hodgkinson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Critical Role ◽  
Biceps Femoris ◽  
Insulin Like Growth Factor ◽  
Gh Treatment ◽  
Factor I ◽  
Significant Difference ◽  
Igf I ◽  
Growth Factor I ◽  
Rna Levels

ABSTRACT Tissue and plasma levels of insulin-like growth factor-I (IGF-I), and relative levels of liver IGF-I RNA, were measured in 6-month-old ewe lambs which were well fed (n = 10) or starved (n = 10) for 5 days. Half of each nutrition group was given daily (09.00 h) injections of human GH (hGH; 0·15 mg/kg body weight per day). Blood was sampled daily from 09.00 to 12.00 h at 15-min intervals through jugular vein catheters and the lambs were slaughtered 24 h after the fifth injection of hGH. Tissue and plasma IGF-I was extracted using an acid-ethanol-cryo-precipitation technique and estimated by radioimmunoassay. Tissue IGF-I was corrected for retained plasma IGF-I using tissue and blood haemaglobin levels. Liver IGF-I RNA levels were monitored by in-situ hybridization. Plasma IGF-I (nmol/l) was higher in both the fed group and the fed group given GH treatment. Tissue IGF-I from kidneys (nmol/kg) was also higher (P < 0·001) in the fed group. There was no significant difference in IGF-I concentrations in the muscle biceps femoris or liver between fed and starved lambs. Although GH treatment did not increase IGF-I levels in tissues significantly, IGF-I RNA levels in liver were increased (P = 0·02) in both fed and starved animals. The relative liver IGF-I RNA levels positively correlated with their corresponding tissue IGF-I levels in the fed group and the fed group given GH treatment. The lack of a significant IGF-I response to GH in tissues may be due to either the time at which tissues were sampled after the GH treatment or the dose of GH administered. However, the higher IGF-I concentrations in plasma and kidney from fed compared with starved animals and the positive correlations between liver IGF-I and IGF-I RNA levels suggest that tissue and plasma IGF-I is regulated by nutrition and GH, with nutrition playing a critical role in the regulation of tissue and plasma IGF-I in normal lambs. Journal of Endocrinology (1993) 136, 217–224

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