scholarly journals Sexual Dimorphism in the Growth Hormone and Insulin-Like Growth Factor Axis at Birth

2003 ◽  
Vol 88 (8) ◽  
pp. 3708-3714 ◽  
Author(s):  
Michael P. P. Geary ◽  
P. Jane Pringle ◽  
Charles H. Rodeck ◽  
John C. P. Kingdom ◽  
Peter C. Hindmarsh
Keyword(s):  
Birth Weight ◽  
Head Circumference ◽  
Mode Of Delivery ◽  
Plasma Concentrations ◽  
Birth Size ◽  
Maternal Height ◽  
Cord Plasma ◽  
Igf I ◽  
Plasma Gh ◽  
Igfbp 3

In rodents and humans there is a sexually dimorphic pattern of GH secretion that influences the serum concentration of IGF-I. Pattern differences can be identified in children, but it is not known how early this difference is established. We studied the plasma concentrations of IGF-I, IGF-II, IGF-binding protein-3 (BP-3), and GH in cord blood taken from the offspring of 1650 singleton Caucasian pregnancies born at term and related these values to birth weight, length, and head circumference. Pregnancies complicated by preterm delivery, antepartum hemorrhage, pregnancy-induced hypertension, preeclampsia, or gestational diabetes and where cigarette smoking continued were excluded, resulting in a cohort of 987. Cord plasma concentrations of IGF-I, IGF-II, and IGFBP-3 were influenced by factors influencing birth size: gestational age at delivery, mode of delivery, maternal height, and parity of the mother. Plasma GH concentrations were inversely related to the plasma concentrations of IGF-I and IGFBP-3; 10.2% of the variability in cord plasma IGF-I concentration and 2.7% for IGFBP-3 was explained by sex of the offspring and parity. None of the factors, apart from maternal height, influenced cord serum IGF-II concentrations (adjusted r2 = 1%). Sex of the baby, mode of delivery, and parity influenced cord serum GH concentrations (adjusted r2 = 2.6%). Birth weight, length, and head circumference measurements were greater in males than females (P < 0.001). Mean cord plasma concentrations of IGF-I (males, 66.4 ± 1.2 μg/liter; females, 74.5 ± 1.3 μg/liter; P < 0.001) and IGFBP-3 (males, 910 ± 13 μg/liter; females 978 ± 13 μg/liter; P < 0.001) were significantly lower in males than females. Cord plasma GH concentrations were higher in males than females (males, 30.0 ± 1.2 mU/liter; females, 26.9 ± 1.1 mU/liter; P = 0.05), but no difference was noted between the sexes for IGF-II (males, 508 ± 6 μg/liter; females, 519 ± 6 μg/liter; P = NS). After adjustment for gestational age, parity, and maternal height, cord plasma concentrations of IGF-I and IGFBP-3 along with sex explained 38.0% of the variability in birth weight, 25.0% in birth length, and 22.7% in head circumference. These data demonstrate that in a group of singleton Caucasian babies born at term, cord plasma IGF-I, IGFBP-3, and GH concentrations relate to birth size, with evidence for sexual dimorphism in the GH-IGF axis.

Effect of high-protein feed supplements on concentrations of growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in plasma and on the amounts of GH and messenger RNA for GH in the pituitary glands of adult rams

1993 ◽  
Vol 138 (3) ◽  
pp. 421-427 ◽  
Author(s):  
I. J. Clarke ◽  
T. P. Fletcher ◽  
C. C. Pomares ◽  
J. H. G. Holmes ◽  
F. Dunshea ◽  
...  
Keyword(s):  
Binding Protein ◽  
Plasma Concentrations ◽  
High Protein ◽  
Mrna Levels ◽  
Igf I ◽  
Pituitary Glands ◽  
Igf Binding ◽  
Plasma Gh ◽  
Igf Binding Protein ◽  
Igfbp 3

ABSTRACT Three groups of mature rams were maintained on diets of hay, hay+2% lupin or hay+2% cowpea for 11 weeks. Serial blood samples were taken at 15-min intervals for 12 h for the determination of GH and IGF-I content by radioimmunoassay and for IGF-binding protein-3 (IGFBP-3) levels by Western blotting. The rams were killed after 77 days of supplementary feeding and their pituitary glands analysed for content of GH and GH mRNA. Mean plasma GH and baseline GH levels were significantly (P<0·01) decreased in the rams fed lupin and cowpea compared with controls fed hay and GH pulse amplitude was significantly (P<0·001) decreased in the group fed the cowpea diet. The frequency of GH pulses was not significantly altered by either treatment. Plasma concentrations of IGF-I were elevated in rams fed lupin (P<0·001) or cowpea (P<0·05). IGFBP-3 levels were not significantly (P>0·05) altered by either treatment. There were no significant differences in pituitary content of GH mRNA but pituitary content of GH was increased in rams fed lupin (P<0·05) and cowpea (P=0·07). In conclusion, a high-protein diet decreases plasma GH levels and increases IGF-I without changing plasma IGFBP-3 levels in rams. Thus ongoing synthesis of GH, as indicated by the mRNA levels, may cause a build up of GH stores in the pituitary gland. Journal of Endocrinology (1993) 138, 421–427

scholarly journals Clinical and biochemical characteristics and bone mineral density of homozygous, compound heterozygous and heterozygous carriers of three novel IGFALS mutations

2017 ◽  
Vol 176 (6) ◽  
pp. 657-667 ◽  
Author(s):  
Emregül Işık ◽  
Belma Haliloglu ◽  
Jaap van Doorn ◽  
Hüseyin Demirbilek ◽  
Sitha A Scheltinga ◽  
...  
Keyword(s):  
Birth Weight ◽  
Head Circumference ◽  
Compound Heterozygous ◽  
Z Score ◽  
Mineral Density ◽  
Ternary Complex Formation ◽  
Igf I ◽  
Heterozygous Carriers ◽  
Low Serum ◽  
Igfbp 3

Objective Acid-labile subunit (ALS) deficiency (ACLSD), caused by homozygous or compound heterozygous IGFALS mutations, is associated with moderate short stature, delayed puberty, low serum IGF-I and ALS and extremely low serum IGFBP-3. Its effect on birth weight, head circumference, bone mineral density (BMD), serum IGF-II and IGFBP-2 is uncertain, as well as the phenotype of heterozygous carriers of IGFALS mutations (partial ACLSD). Design From all available members of five Turkish families, carrying three mutations in exon 2 of IGFALS (c.1462G > A, p.Asp488Asn (families A, B, E); c.251A > G, p.Asn84Ser (families C and E) and c.1477del, p.Arg493fs (family D)), clinical, laboratory and BMD data were collected. Methods Auxological and biochemical findings were expressed as SDS for age and gender. Ternary complex formation in serum was investigated by size-exclusion chromatography. BMD using DXA bone densitometry was adjusted for height and age (Ha-BMD z-score). Results In ACLSD (n = 24), mean ± s.d. height SDS (−2.7 ± 1.2), head circumference SDS (−2.3 ± 0.5) and body mass index (BMI) (−0.6 ± 1.0 SDS) were lower than those in partial ACLSD (n = 26, P ≤ 0.01) and birth weight SDS (n = 7) tended to be lower (−2.2 ± 1.1 vs −0.6 ± 0.3 in partial ACLSD (P = 0.07)). Serum IGF-I was −3.7 ± 1.4 vs −1.0 ± 1.0, IGF-II: −5.6 ± 0.7 vs −1.3 ± 0.7, ALS: <−4.4 ± 1.2 vs −2.1 ± 0.9 and IGFBP-3: −9.0 ± 1.9 vs −1.6 ± 0.8 SDS respectively (P < 0.001). Ha-BMD z-score was similar and normal in both groups. Conclusions To the known phenotype of ACLSD (i.e. short stature, reduced serum levels of IGF-I and ALS, extremely low serum IGFBP-3 and disturbed ternary complex formation), we add reduced birth weight, head circumference and serum IGF-II.

scholarly journals The association of women’s birth size with risk of molecular breast cancer subtypes: a cohort study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Marie S. Sandvei ◽  
Signe Opdahl ◽  
Marit Valla ◽  
Pagona Lagiou ◽  
Ellen Veronika Vesterfjell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Birth Weight ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Head Circumference ◽  
Birth Length ◽  
Birth Size ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Luminal B

Abstract Background Because birth size appears to be positively associated with breast cancer risk, we have studied whether this risk may differ according to molecular breast cancer subtypes. Methods A cohort of 22,931 women born 1920–1966 were followed up for breast cancer occurrence from 1961 to 2012, and 870 were diagnosed during follow-up. Archival diagnostic material from 537 patients was available to determine molecular breast cancer subtype, specified as Luminal A, Luminal B (human epidermal growth factor receptor 2 (HER2)-), Luminal B (HER2+), HER2 type, and Triple negative (TN) breast cancer. Information on the women’s birth weight, birth length and head circumference at birth was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for each molecular subtype, applying Cox regression, and stratified by maternal height. Results Birth length (per 2 cm increments) was positively associated with Luminal A (HR = 1.2, 95% CI, 1.0–1.3), Luminal B (HER2+) (HR = 1.3, 95% CI, 1.0–1.7), and TN breast cancer (HR = 1.4, 95% CI, 1.0–1.9). No clear association was found for birth weight and head circumference. The positive associations of birth length were restricted to women whose mothers were relatively tall (above population median). Conclusion We found a positive association of birth length with risk of Luminal A, Luminal B (HER2+) and TN breast cancer that appears to be restricted to women whose mothers were relatively tall. This may support the hypothesis that breast cancer risk is influenced by determinants of longitudinal growth and that this finding deserves further scrutiny.

scholarly journals Maternal seafood consumption and infant birth weight, length and head circumference in the Norwegian Mother and Child Cohort Study

2011 ◽  
Vol 107 (3) ◽  
pp. 436-444 ◽  
Author(s):  
Anne Lise Brantsæter ◽  
Bryndis Eva Birgisdottir ◽  
Helle Margrete Meltzer ◽  
Helen Engelstad Kvalem ◽  
Jan Alexander ◽  
...  
Keyword(s):  
Cohort Study ◽  
Birth Weight ◽  
Head Circumference ◽  
Birth Size ◽  
Seafood Consumption ◽  
Birth Registry ◽  
Negatively Associated ◽  
Lean Fish ◽  
Mother And Child ◽  
Infant Birth

Results from previous studies on associations between maternal fish and seafood intakes and fetal growth are inconclusive. The aim of the present study was to investigate how maternal intakes of seafood, subtypes of seafood and supplementary n-3 fatty acids were associated with infant birth weight, length and head circumference in a prospective study in Norway. The study population included 62 099 participants in the Norwegian Mother and Child Cohort Study. The mothers answered an FFQ in mid pregnancy. The FFQ comprised detailed questions about intake of various seafood items and n-3 supplements. Data on infant birth weight, length and head circumference were obtained from the Medical Birth Registry. We used multivariable regression to examine how total seafood, various seafood subtypes and supplementary n-3 intakes were associated with birth size measures. Total seafood intake was positively associated with birth weight and head circumference. Lean fish was positively associated with all birth size measures; shellfish was positively associated with birth weight, while fatty fish was not associated with any birth size measures. Intake of supplementary n-3 was negatively associated with head circumference. The relative risk of giving birth to a small baby ( < 2500 g) in full-term pregnancies was significantly lower in women who consumed >60 g/d of seafood than in women who consumed ≤ 5 g/d (OR = 0·56 (95 % CI 0·35, 0·88). In conclusion, maternal seafood consumption was positively associated with birth size, driven by lean fish intake, while supplementary n-3 intake was negatively associated with infant head circumference.

scholarly journals The GH/IGF-I axis in the brushtail possum (Trichosurus vulpecula) pouch young

2003 ◽  
Vol 176 (2) ◽  
pp. 219-225 ◽  
Author(s):  
MC Saunders ◽  
RT Gemmell ◽  
JD Curlewis
Keyword(s):  
Mrna Expression ◽  
Fetal Liver ◽  
Post Partum ◽  
Fold Increase ◽  
High Plasma ◽  
Brushtail Possum ◽  
Trichosurus Vulpecula ◽  
Igf I ◽  
Plasma Gh ◽  
Igfbp 3

Plasma and pituitary GH concentrations and liver GH receptor (GHR), IGF-I and IGF-binding protein-3 (IGFBP-3) mRNA expression were determined in brushtail possum (Trichosurus vulpecula) pouch young aged 12-150 days post-partum and in adults. Mean plasma GH concentrations were highest, measuring around 150 ng/ml, from 12 to 100 days post-partum, and thereafter declined so that by 150 days post-partum levels were not significantly different from those in adults (10.8+/-1.8 ng/ml (S.E.M.)). In contrast to plasma levels, pituitary GH content increased markedly throughout pouch life, with an 87-fold increase between 12 and 150 days post-partum. However, when expressed per gram body weight, pituitary content was relatively constant between 25 and 150 days post-partum, indicating that the decline in plasma GH after 100 days post-partum was not due to decreased synthesis and/or storage of GH in the pituitary gland. Expression of GHR, IGF-I and IGFBP-3 mRNAs was determined by semi-quantitative RT-PCR. Liver GHR and IGF-I mRNA expression were low at 12 and 25 days post-partum and did not show sustained and significant increases (P<0.05) until 125 and 150 days post-partum. IGFBP-3 expression was also low at 12 days post-partum but then increased rapidly to a maximum at 50 days post-partum and thereafter declined. For all three mRNAs, liver expression at day 150 was not significantly different from that in adults. These patterns of gene expression for GHR and IGF-I suggest that the possum liver is resistant to the high plasma GH concentrations during early pouch life and in this way is similar to the fetal liver of some eutherian mammals.

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

Influence of nutritional status and oestradiol-17β on plasma growth hormone, insulin-like growth factors-I and -II and the response to exogenous growth hormone in young steers

1988 ◽  
Vol 118 (2) ◽  
pp. 243-250 ◽  
Author(s):  
B. H. Breier ◽  
P. D. Gluckman ◽  
J. J. Bass
Keyword(s):  
Body Weight ◽  
Dry Matter ◽  
Plasma Concentrations ◽  
Peak Height ◽  
High Affinity ◽  
Oestradiol Treatment ◽  
Igf I ◽  
Plasma Gh ◽  
Somatotrophic Axis ◽  
Insulin Like Growth Factors

ABSTRACT Plasma GH profiles and circulating concentrations of plasma insulin-like growth factors-I and -II (IGF-I and -II) were examined in 20 steers on either high (3% dry matter of body weight per day) or low (1% dry matter of body weight per day) planes of nutrition with or without an implant of oestradiol-17β. The response of plasma IGF-I and -II to a bolus injection of bovine GH (bGH) was also investigated. Reduced feeding significantly (P <0·01) increased the mean concentration, peak height and integrated area of plasma GH. Treatment of steers with oestradiol at low nutrition significantly increased baseline GH concentrations. Treatment of steers with oestradiol at high nutrition significantly (P <0·05) increased mean, baseline, peak height, and integrated area of plasma GH. GH pulse frequency was not changed by either nutritional plane or oestradiol treatment. Basal concentrations of plasma IGF-I were significantly (P <0·01) decreased by reduced feeding in both the oestradiol-treated and the control group. Treatment with oestradiol increased (P <0·01) basal plasma concentrations of IGF-I at both high and low levels of nutrition. After i.v. injection of bGH (0·1 mg/kg body weight), an increase in plasma IGF-I was observed only in steers at high nutrition. Basal concentrations of plasma IGF-II were not altered by nutritional manipulations but were significantly (P <0·001) increased by oestradiol treatment. After bGH infusion only steers at high nutrition showed an increase in plasma IGF-II. Significant correlations were observed between daily body weight gain and plasma concentrations of IGF-I (r= 0·91, P<0·001, n = 20) and also between the capacity of the high-affinity hepatic somatotrophic receptor and plasma IGF-I (r= 0·89, P <0·001, n= 10). Decreased plasma concentrations of IGF-I at a low level of nutrition may abolish the growth-promoting activity of circulating GH. The increase in both GH secretion and the number of somatotrophic receptors with oestradiol treatment may represent a coordinated response of the somatotrophic axis leading to enhanced IGF-I and -II production and improved growth rate. The inferential relationships between the capacity of the high-affinity somatotrophic receptor, plasma concentrations of IGF-I and growth rates suggest that active modulation of somatotrophic receptors is an important regulatory constituent of the somatotrophic axis. J. Endocr. (1988) 118, 243–250

scholarly journals IGF-I, IGF Binding Protein (IGFBP)-3, Phosphoisoforms of IGFBP-1, and Postnatal Growth in Very Low Birth Weight Infants

2002 ◽  
Vol 87 (5) ◽  
pp. 2171-2179 ◽  
Author(s):  
Eero Kajantie ◽  
Leo Dunkel ◽  
Eeva-Marja Rutanen ◽  
Markku Seppälä ◽  
Riitta Koistinen ◽  
...  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Very Low Birth Weight ◽  
Binding Protein ◽  
Postnatal Growth ◽  
Low Birth Weight Infants ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

scholarly journals Protein QTL analysis of IGF-I and its binding proteins provides insights into growth biology

2020 ◽  
Author(s):  
Eric Bartell ◽  
Masanobu Fujimoto ◽  
Jane C. Khoury ◽  
Philip R. Khoury ◽  
Sailaja Vedantam ◽  
...  
Keyword(s):  
Birth Weight ◽  
Association Studies ◽  
Genetic Regulation ◽  
Human Growth ◽  
Serum Levels ◽  
Genome Wide Association Studies ◽  
Genetic Associations ◽  
Protein Levels ◽  
Igf I ◽  
Igfbp 3

AbstractThe growth hormone and insulin-like growth factor (IGF) system is integral to human growth. Genome-wide association studies (GWAS) have identified variants associated with height and located near the genes in this pathway. However, mechanisms underlying these genetic associations are not understood. To investigate the regulation of the genes in this pathway and mechanisms by which regulation could affect growth, we performed GWAS of measured serum protein levels of IGF-I, IGFBP-3, PAPP-A2, IGF-II, and IGFBP-5 in 839 children (3-18 years) from the Cincinnati Genomic Control Cohort. We identified variants associated with protein levels near IGFBP3 and IGFBP5 genes, which contain multiple signals of association with height and other skeletal growth phenotypes. Surprisingly, variants that associate with protein levels at these two loci do not colocalize with height associations, confirmed through conditional analysis. Rather, the IGFBP3 signal (associated with total IGFBP-3 and IGF-II levels) colocalizes with an association with sitting height ratio (SHR); the IGFBP5 signal (associated with IGFBP-5 levels) colocalizes with birth weight. Indeed, height-associated SNPs near genes encoding other proteins in this pathway are not associated with serum levels, possibly excluding PAPP-A2. Mendelian randomization supports a stronger relationship of measured serum levels with SHR (for IGFBP-3) and birth weight (for IGFBP-5) than with height. In conclusion, we begin to characterize the genetic regulation of serum levels of IGF-related proteins in childhood. Furthermore, our data strongly suggest the existence of growth-regulating mechanisms acting through IGF-related genes in ways that are not reflected in measured serum levels of the corresponding proteins.

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