scholarly journals Effects of early gestation GH administration on placental and fetal development in sheep

2008 ◽  
Vol 198 (1) ◽  
pp. 91-99 ◽  
Author(s):  
Casey D Wright ◽  
Ryan J Orbus ◽  
Timothy R H Regnault ◽  
Russell V Anthony
Keyword(s):  
Placental Tissue ◽  
Liver Weight ◽  
Luminal Epithelium ◽  
Gh Treatment ◽  
Igf I ◽  
Uterine Fluid ◽  
Igf Binding ◽  
The Impact ◽  
Twin Pregnancies ◽  
Igfbp 3

Ovine GH (oGH) is synthesized in placental tissue during maximal placental growth and development. Our objectives were to localize oGH mRNA in the placenta, and study the impact of exogenous GH on twin pregnancies during the normal window (35–55 days of gestational age; dGA) of placental expression. In situ hybridization localized oGH mRNA in uterine luminal epithelium but not in tissues of fetal origin. While maternal GH and IGF-I concentrations were increased (P<0.001) approximately tenfold, uterine, uterine fluid, placental, and fetal weights were unaffected by treatment at either 55 or 135 dGA. Fetal length, liver weight, and liver weight per kg of body weight were unaffected by maternal GH treatment. However, in the cotyledon, IGF-binding protein (BP)-1 and IGFBP-4 mRNA concentrations were increased (P<0.05), while IGFBP-2 mRNA was decreased (P<0.05). The concentration of mRNA for IGFBP-3 was unaffected by treatment. Within the caruncle, IGFBP-1 mRNA was decreased (P<0.05), while IGFBP-3 and IGFBP-4 mRNA were increased (P<0.05), and IGFBP-2 mRNA was unchanged due to GH treatment. While our data indicate that elevated maternal GH and IGF-I concentrations during early and mid-gestation do not enhance placental and fetal growth in twin pregnancies, localization of GH mRNA in uterine luminal epithelium could explain GHs transitory expression from 35 to 55 dGA, since by the end of this period the majority of the uterine luminal epithelium has fused with chorionic binucleate cells forming the placental syncytium.

scholarly journals IGFs and IGF-binding proteins in short children with steroid-dependent nephrotic syndrome on chronic glucocorticoids: changes with 1 year exogenous GH

2001 ◽  
pp. 237-243 ◽  
Author(s):  
X Zhou ◽  
KY Loke ◽  
CC Pillai ◽  
HK How ◽  
HK Yap ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Growth Retardation ◽  
Bone Age ◽  
Gh Treatment ◽  
Igf Binding Proteins ◽  
Steroid Dependent ◽  
Igf I ◽  
Igf Binding ◽  
Pre Treatment ◽  
Igfbp 3

OBJECTIVE: Children with steroid-dependent nephrotic syndrome (SDNS), despite being in remission on glucocorticoids, continue to have growth retardation and short stature. The mechanism is uncertain as both chronic glucocorticosteroids and the nephrotic syndrome may independently affect growth. We investigated the changes in the IGFs and IGF-binding proteins (IGFBPs) in a group of short SDNS children, and studied the changes prospectively with 1 year's treatment with GH. DESIGN AND METHODS: Total and 'free' IGF-I, IGFBP-3 and acid-labile subunit (ALS) were studied in eight SDNS boys (mean age=12.6 years; mean bone age=9.1 years) on long term oral prednisolone (mean dose 0.46 mg/kg per day) before, during, and after, 1 year's treatment with GH (mean dose 0.32 mg/kg per week). Pretreatment comparisons were made with two control groups, one matched for bone age (CBA; mean bone age=9.2 years), and another for chronological age (CCA; mean chronological age=13 years). Subsequently, three monthly measurements of serum and urine IGFBPs were carried out in the GH-treated SDNS patients using Western ligand blot and Western immunoblot. RESULTS: Pre-treatment serum total IGF-I levels and the IGF-I/IGFBP-3 ratio were elevated significantly in SDNS compared with CBA, and were similar to CCA. Serum free IGF-I levels were elevated significantly compared with both control groups, but serum IGFBP-3 did not differ significantly. Urinary IGFBP-2, IGFBP-3 and ALS were detectable in the SDNS children only. With GH treatment, IGF-I and IGFBP-3, but not IGF-II, increased significantly compared with pre-treatment values, and returned to baseline after cessation of GH treatment. Urinary IGFBPs did not change significantly with GH treatment. CONCLUSIONS: There is persistent urinary loss of IGFBP-2, IGFBP-3 and ALS in children with SDNS in remission with growth retardation. However, the significant elevation in serum IGF-I suggests that glucocorticoid-induced resistance to IGF is the main factor responsible for the persistent growth retardation in these children. Exogenous GH was able to overcome this resistance by further increasing serum IGF-I.

Differential effects of GH stimulation on fasting and prandial metabolism and plasma IGFs and IGF-binding proteins in lean and obese sheep

1997 ◽  
Vol 154 (2) ◽  
pp. 329-346 ◽  
Author(s):  
J P McCann ◽  
S C Loo ◽  
D L Aalseth ◽  
T Abribat
Keyword(s):  
Binding Proteins ◽  
Binding Capacity ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Daily Injection ◽  
Gh Treatment ◽  
Igf Binding Proteins ◽  
Igf I ◽  
Igf Binding ◽  
Igfbp 3

Abstract The effect of body condition per se on plasma IGFs and IGF-binding proteins (IGFBPs) and the whole-body metabolic responses to recombinant DNA-derived bovine GH (rbGH) in both the fed and the fasted state were determined in lean and dietary obese sheep (n=6/group). Sheep at zero-energy balance and equilibrium body weight were injected s.c. for 12 days with 100 μg/kg rbGH immediately before their morning feeding. Before GH treatment, fasting plasma concentrations of insulin (17·0 ± 1·9 vs 7·5 ± 0·7 μU/ml), IGF-I (345 ± 25 vs 248 ± 10 ng/ml), glucose (52·6 ± 1·1 vs 48·3 ± 0·7 mg/dl), and free fatty acid (FFA) (355 ± 45 vs 229 ± 24 nmol/ml) were greater (P<0·05) and those of GH (1·1 ± 0·2 vs 2·6 ± 0·3 ng/ml) were lower (P<0·05) in obese than in lean sheep. Fasting concentrations of IGF-II and glucagon were not affected (P>0·05) by obesity. GH concentrations were increased equivalently by 6–9 ng/ml in lean and obese sheep during GH treatment. GH caused an immediate and a marked fivefold increase in the fasting insulin level in obese sheep but only minimally affected insulin concentration in lean sheep. The increment in fasting glucose during GH treatment was greater (P<0·05) in obese (8–12 mg/dl) than in lean (2–5 mg/dl) sheep. Frequent measurements in the first 8 h after feeding and injection of excipient (day 0) or the first (day 1), sixth (day 6) and twelfth (day 12) daily injection of GH showed that prandial metabolism in both groups of sheep was affected minimally by GH. However, GH treatment on day 1 (not days 6 or 12) acutely attenuated the feeding-induced suppression of plasma FFA in both groups of sheep and this effect was significantly greater in obese than in lean sheep. Although obese sheep were hyposomatotropic, the basal and GH-induced increases in plasma IGF-I concentrations were greater (P<0·05) in obese than in lean sheep. Plasma IGF-II was unaffected by obesity and was not increased by GH stimulation. Western ligand blotting showed that IGFBP-3 accounted for approximately 50–60% of the plasma IGF-I binding capacity in sheep respectively both before and during GH treatment. Basal plasma levels of IGFBP-2 were lower (P<0·05) and those of IGFBP-3 greater (P<0·05) in obese compared with lean sheep. GH increased the level of IGFBP-3 equally in lean and obese sheep, but suppressed the expression of IGFBP-2 more (P<0·05) in lean than in obese sheep. We concluded that the diabetogenic-like actions of GH in sheep were exaggerated markedly by obesity, and were expressed more during the fasted than the fed states. The effects of GH stimulation on the endocrine pancreas may be selective for β-cells and preferentially enhanced by obesity. GH regulation of IGF-I and the IGFBPs differs in lean and obese sheep. Journal of Endocrinology (1997) 154, 329–346

Growth hormone treatment during pregnancy in a growth hormone-deficient woman

1995 ◽  
Vol 132 (6) ◽  
pp. 727-729 ◽  
Author(s):  
Jørn Müller ◽  
Jørgen Starup ◽  
J Sandahl Christiansen ◽  
Jens OL Jøgensen ◽  
Anders Juul ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Treatment ◽  
Abdominal Ultrasound ◽  
Serum Levels ◽  
Hormone Treatment ◽  
Donor Insemination ◽  
Gh Treatment ◽  
Igf I ◽  
Igf Binding ◽  
Igfbp 3

Müller J, Starup J, Christiansen JS, Jørgensen JOL, Juul A, Skakkebaek NE, Growth hormone treatment during pregnancy in a growth hormone-deficient woman. Eur J Endocrinol 1995;132:727–9. ISSN 0804–4643 Information on the course and outcome of pregnancies in growth hormone (GH)-deficient patients is sparse, and GH treatment during pregnancy in such women has not been described previously. We have studied fetal growth and serum levels of GH, insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) during pregnancy, as well as birth weight and hormone levels after delivery in a 2 5-year-old woman with idiopathic, isolated GH deficiency diagnosed at the age of 7 years. As part of a clinical trial, the patient was treated with 2 IU/M2 GH for a period of 5 years. At this time she became pregnant after donor insemination. The GH treatment was continued until variant GH production from the placenta was evident. Serum levels of GH, IGF-I and IGFBP-3 were measured monthly during pregnancy after 3 days off GH therapy. Abdominal ultrasound was performed five times. Hormonal levels were measured immediately after delivery and during the following days. Serum GH and IGF-I levels increased during the second half of pregnancy: serum IGFBP-3 remained constant throughout pregnancy at a normal level. Serum levels of GH fell within 1 h after delivery, and levels of IGF-I and IGFBP-3 decreased into the range of GH-deficient women 4 days after. The fetal biparietal diameter increased normally, and birthweight was 3.564kg, length 52 cm. No adverse events were recorded. We conclude that the role of GH replacement during pregnancy of GH-deficient women should be investigated further. Jørn Müller, Department of Growth and Reproduction, GR 5064, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen ø, Denmark

scholarly journals IGF-I and IGF-binding protein-3 measurements on filter paper blood spots in children and adolescents on GH treatment: use in monitoring and as markers of growth performance

2003 ◽  
pp. 179-185 ◽  
Author(s):  
U Das ◽  
AJ Whatmore ◽  
J Khosravi ◽  
JK Wales ◽  
G Butler ◽  
...  
Keyword(s):  
Growth Performance ◽  
Children And Adolescents ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Gh Treatment ◽  
Cross Sectional ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

BACKGROUND/AIM: In childhood an appropriate response to GH treatment is achieved by titration of growth response against dose administered, with careful observation for side-effects. In order to evaluate the potential use of IGF monitoring in children treated with GH, a cross-sectional study has been carried in 215 children and adolescents (134 with GH deficiency (GHD), 54 with Turner syndrome (TS) and 27 with non-GHD growth disorders) treated with GH for 0.2-13.7 years. METHODS: IGF-I and IGF-binding protein-3 (IGFBP-3) were measured in ELISAs, using dried capillary blood collected onto filter papers. Results were expressed as the mean S.D. range (SDS). Values of either analyte < -2 or > +2 SDS were considered abnormal. RESULTS: IGF-I and IGFBP-3 SDS were higher in the TS and non-GHD groups (mean +0.01 and +0.1 respectively) than in those with GHD (mean value -0.6). Nineteen per cent of the IGF-I values (13% low, 6% high) and 12% of IGFBP-3 values were abnormal (10% low, 2% high). Abnormalities, either low or high, were most common in the GHD group. There was a weak but significant relationship between change in height SDS over the Year up to the time of sampling in the whole group and IGF-I SDS. Satisfactory growth performance (+0.5>change in height SDS> -0.5) was found in those with high (7.2%), normal (60%) and low (9.3%) IGF-I levels. Overall, it was estimated that 26% of the tests would indicate that an adjustment to GH dose (up in 18% and down in 8%) could be considered. CONCLUSIONS: From this cross-sectional study of IGF monitoring across a broad range of diagnoses and ages, it can be concluded that the majority of children on GH have normal levels of IGF-I and IGFBP-3, but 26% of tests could suggest that a change of GH dose should be considered. Regular monitoring of IGF-I and IGFBP-3 should be considered in any child on GH treatment.

scholarly journals Development of an RIA for salmon 41 kDa IGF-binding protein

2003 ◽  
Vol 178 (2) ◽  
pp. 275-283 ◽  
Author(s):  
M Shimizu ◽  
A Hara ◽  
WW Dickhoff
Keyword(s):  
Coho Salmon ◽  
Molar Ratio ◽  
Gh Treatment ◽  
Igf Binding Proteins ◽  
Igf I ◽  
Igf Binding ◽  
Molecular Masses ◽  
Size Type ◽  
Igf Binding Protein ◽  
Igfbp 3

Salmon plasma contains at least three IGF-binding proteins (IGFBPs) with molecular masses of 41, 28 and 22 kDa. The 41 kDa IGFBP is similar to mammalian IGFBP-3 in size, type of glycosylation and physiological responses. In this study, we developed an RIA for the 41 kDa IGFBP. The 41 kDa IGFBP purified from serum was used for antibody production and as an assay standard. Binding of three different preparations of tracer were examined: (125)I-41 kDa IGFBP, (125)I-41 kDa IGFBP cross-linked with IGF-I and 41 kDa IGFBP cross-linked with (125)I-IGF-I (41 kDa IGFBP/(125)I-IGF-I). Only binding of 41 kDa IGFBP/(125)I-IGF-I was not affected by added IGFs, and therefore it was chosen for the tracer in the RIA. Plasma 41 kDa IGFBP levels measured by RIA were increased by GH treatment (178.9+/-4.9 ng/ml) and decreased after fasting (95.0+/-7.0 ng/ml). The molarities of plasma 41 kDa IGFBP and total IGF-I were comparable, and they were positively correlated, suggesting that salmon 41 kDa IGFBP is a main carrier of circulating IGF-I in salmon, as is mammalian IGFBP-3 in mammals. During the parr-smolt transformation (smoltification) of coho salmon, plasma 41 kDa IGFBP levels showed a transient peak (182.5+/-10.3 ng/ml) in March and stayed relatively constant thereafter, whereas IGF-I showed peak levels in March and April. Differences in the molar ratio between 41 kDa IGFBP and IGF-I possibly influence availability of IGF-I in the circulation during smoltification.

scholarly journals SUN-LB61 Differential and Opposite Regulation of Acid Labile Subunit (ALS) Versus Insulin-Like Growth Factor I (IGF-I) by Oral Estrogens in Premenopausal Women

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Katharina Schilbach ◽  
Michael Haenelt ◽  
Shiva Sophia Nicolay ◽  
Laura Schwerdt ◽  
Rita Schwaiger ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Negative Correlation ◽  
Premenopausal Women ◽  
Oral Contraception ◽  
Limit Of Quantification ◽  
Igf I ◽  
Igf Binding ◽  
Post Hoc ◽  
The Impact ◽  
Igfbp 3

Abstract Background: The impact of estrogens (E2) on the growth hormone (GH)/IGF-I axis is known to depend on route of administration: While oral E2 increases GH and decreases IGF-I, transdermal E2 has only limited or no effect. However, data concerning the impact of E2 on IGF binding protein 3 (IGFBP 3) and ALS are less clear. One study in girls demonstrated higher ALS with oral E2, while the opposite was suggested for postmenopausal women. No data are available for healthy premenopausal women.Methods: We measured IGF-I, IGFBP 3 and ALS in fasted healthy adults (93 males (M), 35 premenopausal women without E2-containing oral contraception (FPRE), 37 premenopausal women with E2-containing oral contraception (FPREOC) and 34 postmenopausal women (FPOST)). IGF-I and IGFBP 3 were measured using the IDS-iSYS chemiluminescence immunoassay, and ALS by an in-house immunofluorometric assay (limit of quantification (LoQ) &lt; 50 mU/ml, range 50 - 4000 mU/mL).Results: Median age (range) was 33 (20 - 76), 28 (20 - 44), 24 (21 - 36) and 56 (49 - 70) years for M, FPRE, FPREOC and FPOST, respectively. As expected, IGF-I was lower in FPREOC compared to FPRE (median IGF-I xULN (IQR) 0.56 (0.45 - 0.73) and 0.72 (0.63 – 0.80), P = 0.0017, Kruskal-Wallis). ALS was significantly higher in FPREOC compared to all other groups (mean ALS in M, FPRE, FPREOC and FPOST: 636, 708, 861 and 648 mU/mL, respectively, ANOVA P &lt; 0.0001, Dunnett’s post-hoc test: M vs FPREOC: P &lt; 0.0001, FPRE vs FPREOC: P = 0.0007, FPOST vs FPREOC: P &lt; 0.0001). IGFBP 3 was not different in females with and without oral E2 (median IGFBP 3 xULN (IQR) FPREOC vs FPRE: 0.62 (0.54 - 0.67) vs 0.60 (0.49 – 0.76), Kruskal-Wallis P = 0.295, Dunn’s post-hoc test: P &gt; 0.9999). This was also true between all other groups (Dunn’s post-hoc test: P ≥ 0.4). In our adult cohort, ALS exhibited negative correlation with age (Pearson r = -0.282, P = 0.0003), similar to IGF-I and IGFBP 3. While IGF-I exhibited a moderate negative correlation to BMI (Pearson r = -0.25, P = 0.0013), IGFBP 3 and ALS were not significantly related to BMI.Conclusion: While IGF-I, IGFBP 3 and ALS all are known to be secreted in response to GH, and IGF-I and ALS are assumed to be produced by the same cells in the liver (hepatocytes), the three GH dependent biomarkers appear to be differently regulated by metabolic factors and oral E2. Only IGF-I has some modest association with BMI. Oral E2 is associated with reduced IGF-I, unchanged IGFBP 3 but increased ALS. While the mechanism behind the differential regulation remains to be uncovered, E2 therapy must be taken into account when interpreting IGF-I and ALS concentrations.

Specimen processing time and measurement of total insulin-like growth factor-I (IGF-I), free IGF-I, and IGF binding protein-3 (IGFBP-3)

2006 ◽  
Vol 16 (2) ◽  
pp. 86-92 ◽  
Author(s):  
Tiffany G. Harris ◽  
Howard D. Strickler ◽  
Herbert Yu ◽  
Michael N. Pollak ◽  
E. Scott Monrad ◽  
...  
Keyword(s):  
Growth Factor ◽  
Processing Time ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Specimen Processing ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

scholarly journals Dexamethasone administration attenuates the inhibitory effect of lipopolysaccharide on IGF-I and IGF-binding protein-3 in adult rats

2005 ◽  
Vol 185 (3) ◽  
pp. 467-476 ◽  
Author(s):  
Teresa Priego ◽  
Miriam Granado ◽  
Ana Isabel Martín ◽  
Asunción López-Calderón ◽  
María Angeles Villanúa
Keyword(s):  
Gene Expression ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Serum Concentrations ◽  
Gh Receptor ◽  
Its Gene ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

The aim of this study was to investigate whether glucocorticoid administration had a beneficial effect on serum concentrations of insulin-like growth factor I (IGF-I) and on IGF-binding protein 3 (IGFBP-3) in rats injected with lipopolysaccharide (LPS). Adult male rats were injected with LPS or saline and pretreated with dexamethasone or saline. Dexamethasone administration decreased growth hormone (GH) receptor and IGF-I mRNA levels in the liver of control rats. LPS decreased GH receptor and IGF-I gene expression in the liver of saline-treated rats but not in the liver of dexamethasone-pretreated rats. In the kidney, GH receptor mRNA levels were not modified by dexamethasone or LPS treatment. However, LPS decreased renal IGF-I gene expression and dexamethasone pretreatment prevented this decrease. Serum concentrations of IGF-I were decreased by LPS, and dexamethasone pretreatment attenuated this effect. The gene expression of IGFBP-3 in the liver and kidney and its circulating levels were decreased by LPS. In control rats dexamethasone increased circulating IGFBP-3 and its gene expression in the liver, and decreased the proteolysis of this protein. Dexamethasone pretreatment attenuated the LPS-induced decrease in IGFBP-3 gene expression in the liver and prevented the LPS-induced decrease in IGFBP-3 gene expression in the kidney. Moreover, dexamethasone pretreatment attenuated the LPS-induced decrease in serum concentrations of IGFBP-3 and decreased the LPS-induced IGFBP-3 proteolysis in serum. In conclusion, dexamethasone pretreatment partially attenuates the inhibitory effect of LPS on serum IGF-I by blocking the decrease of its gene expression in the kidney as well as by attenuating the decrease in serum concentrations of IGFBP-3.

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