Effects of insulin-like growth factor-I (IGF-I) infusion and dietary tri-iodothyronine (T3) supplementation on growth, body composition and plasma hormone levels in sex-linked dwarf mutant and normal chickens

1992 ◽  
Vol 133 (1) ◽  
pp. 101-110 ◽  
Author(s):  
M. Tixier-Boichard ◽  
L. M. Huybrechts ◽  
E. Decuypere ◽  
E. R. Kühn ◽  
J.-L. Monvoisin ◽  
...  
Keyword(s):  
Body Composition ◽  
Body Weight ◽  
Growth Factor ◽  
Bone Growth ◽  
Dwarf Mutant ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Plasma Hormone ◽  
Plasma Gh

ABSTRACT This study used a sex-linked dwarf mutant (SLD) chicken to evaluate growth-promoting and metabolic effects of recombinant human insulin-like growth factor-I (rhIGF-I) treatment. The SLD chicken is characterized by a 30% reduction in body weight and by high plasma GH levels, low plasma IGF-I and triiodothyronine (T3) levels and very low GH binding on liver membranes, suggesting reduced functional GH receptors compared with normal chickens. The effects of a continuous s.c. infusion by osmotic mini-pump of 0·1 mg rhIGF-I/kg per day from 4 to 8 weeks of age on body weight, bone growth and body composition were investigated in female SLD and normal chicks. In addition, half of the birds received a dietary supplement of T3 (0·1 parts per million). Plasma levels of IGF-I, GH, T3, thyroxine and insulin were followed during the treatment. In normal chicks, rhIGF-I infusion had no effect on growth and little effect on plasma hormone levels except for a decrease in plasma insulin. In dwarf chicks, rhIGF-I infusion slightly increased body weight but had no effect on longitudinal bone growth. In addition, plasma GH levels were decreased and T3 levels remained lower than in normal chicks. Normal and dwarf chicks showed a decrease in abdominal fat after both IGF-I administration and T3 supplementation, the treatments having additive effects in dwarf chicks only. The combined rhIGF-I and T3 treatment restored a quasi-normal hormonal pattern in dwarf chicks, except for insulin which remained lower than in normal chicks. These results suggest that IGF-I in the chicken has no direct endocrine effect on statural growth. Journal of Endocrinology (1992) 133, 101–110

Developmental patterns of plasma insulin-like growth factor-I (IGF-I) and body growth in mice from lines divergently selected on the basis of plasma IGF-I

1990 ◽  
Vol 124 (1) ◽  
pp. 151-158 ◽  
Author(s):  
R. A. Siddiqui ◽  
H. T. Blair ◽  
S. N. McCutcheon ◽  
D. D. S. Mackenzie ◽  
P. D. Gluckman ◽  
...  
Keyword(s):  
Body Composition ◽  
Body Weight ◽  
Growth Factor ◽  
Plasma Concentrations ◽  
Body Growth ◽  
Insulin Like Growth Factor ◽  
Developmental Patterns ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

ABSTRACT A study was conducted to investigate developmental patterns of plasma concentrations of insulin-like growth factor-I (IGF-I), body growth and body composition in mice from lines selected for seven generations on the basis of low (L) or high (H) plasma IGF-I, and in a random-bred control (C) line. Litter size was standardized to eight individuals with equal sex ratios (as far as possible) within 48 h of birth. Pups were weaned at an average of 21 days and separated on the basis of sex. Blood samples were collected from one male and one female of each litter on days, 21, 42, 63 and 105 for analysis of plasma concentrations of IGF-I. The animals were then killed and analysed for water, fat and crude protein content. The plasma concentration of IGF-I was influenced by line (P<0·05) but not by sex. Significant (P< 0·001) differences in liveweight between mice from L and H lines were first evident at 21 days of age. From 28 until 105 days of age the H line was significantly (P< 0·001) heavier than both L and C lines, but differences between C and L lines were inconsistent and mostly non-significant. The growth velocity of the H line was significantly greater than that of C or L lines between 14 and 42 days of age, but differences in growth velocities of C compared with L lines were generally non-significant. Nose–anus length was significantly (P<0·01) affected by sex and line from 42 to 105 days of age, but anus–tail length was not affected by sex or line at any age. Effects of sex and line on empty (digesta-free) body weight and wet weights of carcass and skin plus viscera fractions followed a pattern similar to those of liveweights. The effects of sex and line on protein, water and fat content also paralleled their effects on body size. Differences between males and females, and between the lines, in amount of protein, water and fat could be entirely accounted for by the corresponding differences in body weight. It is concluded from these results that divergent selection on the basis of plasma IGF-I at 42 days of age resulted in lines of animals differing in plasma IGF-I from 21 days of age until maturity. These divergent concentrations of IGF-I are associated with differences between the lines in body growth, particularly during the period of accelerated growth at puberty, but not with changes in body composition. Journal of Endocrinology (1990) 124, 151–158

Influence of nutrition and bovine growth hormone (GH) on hepatic GH binding, insulin-like growth factor-I and growth of lambs

1991 ◽  
Vol 128 (2) ◽  
pp. 181-186 ◽  
Author(s):  
J. J. Bass ◽  
J. M. Oldham ◽  
S. C. Hodgkinson ◽  
P. J. Fowke ◽  
H. Sauerwein ◽  
...  
Keyword(s):  
Body Composition ◽  
Body Weight ◽  
Growth Factor ◽  
Plasma Glucose ◽  
Specific Binding ◽  
Plasma Concentrations ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

ABSTRACT The effect on young lambs of 0·25 mg recombinant bovine GH (bGH)/kg per day on plasma concentrations of insulin-like growth factor-I (IGF-I), glucose, specific hepatic GH binding and body composition changes was examined at two levels of nutrition (lucerne pellets; 3 and 1·7% of body weight/day). Lambs on low levels of nutrition had low plasma IGF-I (P < 0·001). Plasma concentrations of IGF-I were increased by bGH treatment at both levels of nutrition, with the high nutrition group showing the greatest IGF-I response after 3 and 40 days of bGH treatment. Plasma glucose, after 40 days, was higher overall (P < 0·05) in lambs on high nutrition. bGH treatment increased plasma glucose, with the response being greater in the well-fed lambs. Specific binding of GH to liver membranes was highest in lambs on high nutrition and on bGH treatment; no significant interaction between nutrition and bGH treatment was detected, indicating that specific binding of GH was increased proportionally by bGH at both nutritional levels. The major change in body composition was the reduced level of fatness in lambs treated with bGH. There was no significant effect of bGH on body weight although bGH treatment tended to increase weight gain of well-fed lambs and decreased weight loss of poorly nourished lambs. The results show that, although there was a significant (P < 0·05) bGH/nutrition interaction for IGF-I there was no such interaction for body weight/components or specific GH binding to the liver. The results indicate that an increase in plasma IGF-I does not necessarily result in increases in growth or changes in carcass composition. Journal of Endocrinology (1991) 128, 181–186

Growth hormone deficiency in 'little' mice results in aberrant body composition, reduced insulin-like growth factor-I and insulin-like growth factor-binding protein-3 (IGFBP-3), but does not affect IGFBP-2, -1 or -4

1993 ◽  
Vol 136 (1) ◽  
pp. 91-104 ◽  
Author(s):  
L. R. Donahue ◽  
W. G. Beamer
Keyword(s):  
Body Composition ◽  
Growth Factor ◽  
Gh Deficiency ◽  
Body Water ◽  
Insulin Like Growth Factor ◽  
Gh Therapy ◽  
Factor I ◽  
Igf I ◽  
Body Compartments ◽  
Igfbp 3

ABSTRACT Although GH is known to regulate somatic growth during development, its role in regulating adult body composition is less well defined. The effects of GH on individual body compartments – water, fat, protein and mineral – are achieved both by the action of GH and by a GH-induced hormone, insulin-like growth factor-I (IGF-I). We used a genetic model of GH deficiency, the 'little' (gene symbol lit) mouse, to determine the GH regulation of IGF-I and its insulin-like growth factor-binding proteins (IGFBPs) and to define the interaction between these hormones and each body compartment in adults. Our results showed that GH-deficient lit/lit mice had reduced levels of serum IGF-I (range 38–130 μg/l) compared with normal lit/+ littermates (range 432–567 μg/l) between 2 and 52 weeks of age. The lit/lit mice did not experience the fivefold increase in IGF-I between 2 and 4 weeks of age that was seen in lit/+ mice. In lit/lit serum, overall binding of 125I-labelled IGF-I to the four IGFBPs was reduced, solely in response to a reduced amount of IGFBP-3. No overall differences were found between lit/lit and lit/+ mice in the binding of 125I-labelled IGF-I to IGFBP-2, -1 or -4. Age-related declines in IGF-I and IGFBPs were seen in lit/lit mice. However, adult levels of IGF-I were maintained in lit/+ mice to at least 52 weeks of age, as were levels of IGFBP-1 and -4, while IGFBP-3 and -2 declined with age. With respect to body composition, comparison of lit/lit with lit/+ mice showed that the lit/lit mice were characterized by abnormally large adipose tissue stores and reduced body water, protein and mineral from 2 weeks onward. These changes occurred despite normal energy intake in lit/lit mice up to 52 weeks of age, indicating that neither undernutrition nor hyperphagia is characteristic of this GH-induced model of obesity. Furthermore, lit/lit males accrued more body fat beginning at an earlier age than lit/lit females. With advancing age, the per cent body fat increased in both lit/lit and lit/+ mice, while the per cent body water and mineral declined. In lit/lit but not lit/+ mice, per cent protein also declined with age. The changes in body water and fat are attributable to lack of adequate GH in the genetically GH-deficient lit/lit mouse. On the other hand, the changes in body protein are more likely to be effects of IGF-I. Changes in mineral observed in lit/lit mice could be the result of action by GH, IGF-I or both hormones. Therefore, when GH is chronically manipulated by GH deficiency as in lit/lit mice, by GH excess as in acromegaly, or by GH therapy, all four body compartments are affected, suggesting that GH therapy is most valuable when the treatment goal is to alter overall body composition. Journal of Endocrinology (1993) 136, 91–104

Longitudinal bone growth in vitro: effects of insulin-like growth factor I and growth hormone

1991 ◽  
Vol 124 (5) ◽  
pp. 602-607 ◽  
Author(s):  
Ben A. A. Scheven ◽  
Nicola J. Hamilton
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Bone Growth ◽  
Long Bone ◽  
Long Bones ◽  
Insulin Like Growth Factor ◽  
Serum Free ◽  
Factor I ◽  
Igf I

Abstract. Longitudinal growth was studied using an in vitro model system of intact rat long bones. Metatarsal bones from 18- and 19-day-old rat fetuses, entirely (18 days) or mainly (19 days) composed of chondrocytes, showed a steady rate of growth and radiolabelled thymidine incorporation for at least 7 days in serum-free media. Addition of recombinant human insulin-like growth factor-I to the culture media resulted in a direct stimulation of the longitudinal growth. Recombinant human growth hormone was also able to stimulate bone growth, although this was generally accomplished after a time lag of more than 2 days. A monoclonal antibody to IGF-I abolished both the IGF-I and GH-stimulated growth. However, the antibody had no effect on the growth of the bone explants in control, serum-free medium. Unlike the fetal long bones, bones from 2-day-old neonatal rats were arrested in their growth after 1-2 days in vitro. The neonatal bones responded to IGF-I and GH in a similar fashion as the fetal bones. Thus in this study in vitro evidence of a direct effect of GH on long bone growth via stimulating local production of IGF by the growth plate chondrocytes is presented. Furthermore, endogenous growth factors, others than IGFs, appear to play a crucial role in the regulation of fetal long bone growth.

Ovarian and hepatic insulin-like growth factor-I gene expression and associated metabolic responses in prepubertal gilts subjected to feed restriction and refeeding

1993 ◽  
Vol 139 (1) ◽  
pp. 143-152 ◽  
Author(s):  
S. T. Charlton ◽  
J. R. Cosgrove ◽  
D. R. Glimm ◽  
G. R. Foxcroft
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Follicular Fluid ◽  
Feed Restriction ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Plasma Gh ◽  
I Gene

ABSTRACT The effects of feed restriction and refeeding on ovarian and hepatic insulin-like growth factor-I (IGF-I) gene expression, systemic and ovarian IGF-I concentrations and on associated metabolic changes were measured in prepubertal gilts. Eleven pairs of littermate gilts (70·7 ± 4·7 kg) were placed on a maintenance level of feeding for 7 days (days 1–7). On day 8, littermates were either fed at a maintenance level of energy or fed to appetite for a further 6 days. Blood samples were taken on day 13 (07.00–16.00 h) to determine plasma insulin and IGF-I, and on day 14 (02.00–06.00 h) to determine plasma GH levels. Following slaughter on day 14, one ovary from each animal was retained to measure follicular fluid IGF-I and oestradiol concentrations. The remaining ovary and a sample of liver were retained for IGF-I mRNA analysis using a ribonuclease protection assay. Six days of refeeding significantly increased plasma IGF-I (P<0·005) and basal insulin (P<0·05) but there was no effect on plasma GH. Ovarian follicular volume and diameter were significantly larger after refeeding (P<0·05), with no effect on follicular fluid oestradiol concentrations. Mean follicular fluid IGF-I concentrations were unaffected by treatment. However, the relationships between individual follicular IGF-I concentrations, absolute follicular fluid IGF-I contents and follicle volume were affected by feeding level (P<0·05). Regression analysis of the same data also revealed that at this stage of maturity, small follicles had greater follicular fluid concentrations of IGF-I than larger follicles. Refeeding increased the amount of IGF-I mRNA in hepatic but not ovarian tissue. We conclude that there is differential regulation of the IGF-I gene in porcine hepatic and ovarian tissues, and that ovarian factors other than, or as well as, IGF-I are involved in the regulation of ovarian responses to refeeding. Journal of Endocrinology (1993) 139, 143–152

Effects of full-length and truncated insulin-like growth factor-I on nitrogen balance and muscle protein metabolism in nitrogen-restricted rats

1991 ◽  
Vol 128 (1) ◽  
pp. 97-105 ◽  
Author(s):  
F. M. Tomas ◽  
S. E. Knowles ◽  
P. C. Owens ◽  
L. C. Read ◽  
C. S. Chandler ◽  
...  
Keyword(s):  
Body Weight ◽  
Growth Factor ◽  
Muscle Protein ◽  
Analysis Of Covariance ◽  
High Dose ◽  
Insulin Like Growth Factor ◽  
Body Protein ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

ABSTRACT The ability of insulin-like growth factor-I (IGF-I) to protect against losses of body protein during periods of dietary nitrogen restriction has been evaluated in young rats. Recombinant human IGF-I was administered by osmotic pumps at dose rates of 0, 1·2 or 2·9 mg/kg per day over a 7-day period beginning with the transfer of animals from an 18% to a 4% protein diet. A fourth group received the potent truncated IGF-I analogue, des(1–3)IGF-I, at a dose of 1·2 mg/kg per day over a comparable 7-day period. Plasma IGF-I levels were reduced by 60% following nitrogen restriction, a reduction that was partly prevented by IGF-I administration, especially at the higher dose, but not measurably by des(1–3)IGF-I. The major IGF-binding protein circulating in blood, IGFBP-3, demonstrated a similar pattern of change. A significant (P<0·05) protection of body weight was achieved in the low dose IGF-I and des(1–3)IGF-I groups, but only after differences in food intake had been eliminated by analysis of covariance. Nitrogen balances were not significantly different unless analysis of covariance was used to adjust for the nitrogen intakes, whereupon all treatment groups showed improved balance, especially the animals treated with the low IGF-I dose and des(1–3)IGF-I (both P<0·01). The rate of muscle protein breakdown calculated from the urinary excretion of 3-methylhistidine was not significantly altered by the treatments, but fell progressively throughout the 7 days. The fractional rate of muscle protein synthesis measured on the final day was increased by 31, 26 and 21% respectively by the low and high doses of IGF-I and by des(1–3)IGF-I. Organ weights (g/kg body weight) showed no effects of IGF-I treatment except for 16% increases in the weight of kidneys in the high dose IGF-I and the des(1–3)IGF-I groups. Carcass analyses demonstrated higher water and lower fat contents (all P< 0·01) in the same groups. These results suggest that exogenous IGF-I and especially des(1–3)IGF-I can partly protect body protein reserves during nitrogen restriction. Journal of Endocrinology (1991) 128, 97–105

scholarly journals Effects of Human Growth Hormone, Insulin-Like Growth Factor I, and Diet and Exercise on Body Composition of Obese Postmenopausal Women1

1998 ◽  
Vol 83 (5) ◽  
pp. 1477-1484 ◽  
Author(s):  
J. L. Thompson ◽  
G. E. Butterfield ◽  
U. K. Gylfadottir ◽  
J. Yesavage ◽  
R. Marcus ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Composition ◽  
Growth Factor ◽  
Muscle Strength ◽  
Postmenopausal Women ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Diet And Exercise ◽  
Igf I ◽  
Growth Factor I

To determine the effects of GH and insulin-like growth factor I (IGF-I) administration, diet, and exercise on weight loss, body composition, basal metabolic rate (BMR), muscle strength, and psychological status, 33 moderately obese postmenopausal women (67.1 ± 5.2 yr) participated in a 12-week randomized, double blind study. Participants were placed on a diet that provided 500 Cal/day less than that needed for weight maintenance, and they walked 3 days and strength trained 2 days each week. Subjects also self-injected GH (0.025 mg/kg BW·day), IGF-I (0.015 mg/kg BW·day), a combination of these doses of GH and IGF-I, or placebo (P). Twenty-eight women completed the study, as five subjects dropped out due to intolerable side-effects (e.g. edema). Weight loss occurred in all groups, with the largest decrease occurring in the GH plus IGF-I group (5.6 ± 1.4 kg). Fat mass significantly decreased in all groups, with the largest losses observed in GH and GH plus IGF-I groups (6.3 ± 1.8 and 8.4 ± 2.8 kg, respectively). Despite weight loss, BMR was maintained in all groups. Muscle strength increased with training for all groups, and depression and anxiety scores decreased in groups receiving IGF-I. These data show that obese postmenopausal women can lose weight and fat without compromising fat free mass, BMR, or gains in muscle strength, and that GH and IGF-I given together may enhance fat loss over either given alone.

Inhibition of neonatal rat growth and circulating concentrations of insulin-like growth factor-I using an antiserum to rat growth hormone

1989 ◽  
Vol 122 (1) ◽  
pp. 79-86 ◽  
Author(s):  
D. J. Flint ◽  
M. J. Gardner
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Growth Factor ◽  
Body Weight Gain ◽  
Neonatal Rat ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Rat Growth ◽  
Growth Factor I

ABSTRACT Treatment of rats for 24 h on day 2, 10 or 20 of age with a specific antiserum to rGH (anti-(rGH)), GH, bromocriptine (CB-154) or prolactin failed to influence body weight gain or serum concentrations of insulin-like growth factor-I (IGF-I). On day 28 of age, however, anti-(rGH) completely inhibited body weight gain and markedly reduced circulating IGF-I concentrations, effects which were completely prevented by exogenous ovine GH (oGH). When administered to control rats on day 28 oGH caused supranormal weight gain and serum IGF-I concentrations. These results suggested that GH does not play a significant role in growth or regulation of serum IGF-I until after day 20 of age. By contrast, when anti-(rGH) was given for 4 consecutive days beginning on day 2 of life, body weight gain was reduced within 48 h and remained so until at least 28 days of age. Tail length was also significantly reduced. The effect was due to inhibition of GH effects since serum GH concentrations were low and exogenous GH prevented the effect. Inhibition of growth during the first 14 days of life occurred in the absence of any effect on serum IGF-I although by 21 days of age serum IGF-I was considerably lower than in control rats. The prolonged reduction in growth after treatment has stopped appeared to be due to a cytotoxic effect on the pituitary gland since pituitary weight and GH but not prolactin content were significantly decreased. The data are consistent with the hypothesis that in the neonate GH may be processed in serum so that a proportion of it is not recognized by an antiserum to pituitary GH. It would appear that inhibition of GH secretion reduces growth rate by at least 30–40% up to 14 days of age, 50% by 21 days of age and completely by 28 days. Effects of GH on growth could not be fully explained by regulation of serum IGF-I concentrations. Journal of Endocrinology (1989) 122, 79–86

scholarly journals Recombinant Human Insulin-Like Growth Factor I Has Significant Anabolic Effects in Adults with Growth Hormone Receptor Deficiency: Studies on Protein, Glucose, and Lipid Metabolism*

2000 ◽  
Vol 85 (9) ◽  
pp. 3036-3042 ◽  
Author(s):  
Nelly Mauras ◽  
Victor Martinez ◽  
Annie Rini ◽  
Jaime Guevara-Aguirre
Keyword(s):  
Body Composition ◽  
Growth Factor ◽  
Replacement Therapy ◽  
Indirect Calorimetry ◽  
Fat Oxidation ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Gh Receptor ◽  
Intermediate Metabolism ◽  
Igf I

Abstract The physiological effects of insulin-like growth factor I (IGF-I) on intermediate metabolism of substrates have been extensively studied in a variety of experimental situations in man, and its effects on linear growth of children with GH receptor mutations have proven beneficial. However, there is a paucity of data on the metabolic effects of IGF-I as replacement therapy in adults with GH receptor deficiency (Laron’s syndrome). We designed these studies to investigate the in vivo effects of 8 weeks of therapy with recombinant human IGF-I (rhIGF-I) in a unique group of 10 adult subjects with profound IGF-I deficiency due to a mutation in the GH receptor gene (mean ± sem age, 29.2 ± 2.0 yr; 4 males and 6 females). At baseline, patients had infusions of stable tracers, including l-[13C]leucine,[ 2H2]glucose, and d5-glycerol, as well as indirect calorimetry, assessment of body composition (dual energy x-ray absortiometry), and measurements of growth factor concentrations. Patients were then discharged to receive twice daily rhIGF-I (60μ g/kg, sc) for the next 8 weeks when the studies were repeated identically. Plasma IGF-I concentrations increased during rhIGF-I treatment from 9.3 ± 1.5 μg/L to 153 ± 23 (P = 0.0001). There was no change in weight during these studies, but a significant change in body composition was observed, with a decrease in percent fat mass (P = 0.003) and an increase in lean body mass (P = 0.001). These were accompanied by increased rates of protein turnover, decreased protein oxidation, and increased rates of whole body protein synthesis, as measured by leucine tracer methods (P &lt; 0.01). These results are similar to those observed in GH-deficient subjects treated with GH. All measures of lipolytic activity and fat oxidation increased during treatment, with an 18% increase in the glycerol turnover rate (P = 0.04), an increase in free fatty acid andβ -hydroxybutyrate concentrations, and a significant increase in fat oxidation, as measured by indirect calorimetry (P = 0.04). There were significant decreases in insulin concentrations (P = 0.01) and a reciprocal increase in glucose production rates (P = 0.04) during rhIGF-I, yet plasma glucose concentrations remained constant, suggestive of a significant insulin-like action of this peptide. RhIGF-I was well tolerated by all patients. In conclusion, 8 weeks of treatment with rhIGF-I had significant positive effects on body composition and measures of intermediate metabolism independent of GH. These results suggest that, similar to GH treatment of adults with GH deficiency, rhIGF-I may be beneficial as long term replacement therapy for the adult patient with Laron’s syndrome.

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