IGF-I and IGF-binding protein gene expressions in spontaneous dwarf rat

1994 ◽  
Vol 267 (3) ◽  
pp. E396-E401 ◽  
Author(s):  
H. Nogami ◽  
T. Watanabe ◽  
S. Kobayashi
Keyword(s):  
Binding Protein ◽  
Mrna Level ◽  
Pituitary Hormones ◽  
Acute Administration ◽  
Gene Expressions ◽  
Igf I ◽  
Igf Binding ◽  
Normal Rat ◽  
Igf Binding Protein ◽  
Serum Gh

Effects of growth hormone (GH) and fasting on hepatic expressions of insulin-like growth factor I (IGF-I) and IGF-I-binding protein (IGFBP)-1, -2, -3, and -4 were examined in spontaneous dwarf rats (SDR), which completely and specifically lack GH among pituitary hormones. The hepatic expressions of mRNA encoding IGF-I and IGFBP-3 were reduced and IGFBP-1 mRNA was elevated in the SDR. Both chronic and acute administration of GH restored these changes, indicating the association of GH but not other pituitary hormones with hepatic expressions of these genes. In addition, the present examination revealed that mRNA level of IGFBP-2 was elevated in SDR, which could not be attenuated by exogenous GH, and that GH may not be directly relevant to the regulation of hepatic IGFBP-4 expression. Fasting for 2 days reduced IGF-I mRNA level and increased IGFBP-2 mRNA level in the SDR, as well as in the normal rat, suggesting the presence of factors other than reduced serum GH responsible for fasting-induced alteration in the expression of these mRNAs. On the other hand, fasting resulted in little change or even a reduction of IGFBP-1 mRNA level in the SDR.

Moderate food restriction reduces serum IGF-I and alters circulating IGF-binding protein profiles in lactating rats

1997 ◽  
Vol 152 (2) ◽  
pp. 303-316 ◽  
Author(s):  
M H Monaco ◽  
S M Donovan
Keyword(s):  
Body Weight ◽  
Mammary Gland ◽  
Food Restriction ◽  
Binding Protein ◽  
Igf I ◽  
Pregnancy And Lactation ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Serum Gh ◽  
Igfbp 3

Abstract The role of somatogenic and lactogenic hormones in the adaptative mechanisms which occur in response to nutrient restriction during lactation is unknown. To characterize the effect of food restriction during lactation on serum IGF-I, GH and prolactin concentrations and serum IGF-binding protein (IGFBP) profiles, lactating dams had free access to food (control) or were restricted to 60% of control intake during pregnancy and lactation (RPL) or only during lactation (RL). Serum, milk and mammary gland samples were collected throughout lactation. RL dams lost body weight, control dams gained weight, while RPL dams maintained body weight during lactation. By day 20, body and mammary gland weights of RL and RPL dams did not differ and were lower than control (P<0·05). Serum IGF-I concentrations in restricted groups were lower than control (P<0·05), however, hepatic expression of IGF-I mRNA did not differ between groups in early (day 1) or mid-lactation (day 8) and was increased on day 20 in RL dams compared with RPL or control. These data suggest that serum IGF-I and hepatic IGF-I mRNA expression are not co-ordinately regulated in the food-restricted lactating rat. In early lactation, serum IGFBP-3 was lower in RPL dams than control (P<0·05), whereas IGFBP-1 and -2 were increased in RL and RPL dams in late lactation compared with control. The decrease in IGFBP-3 and increase in lower molecular weight IGFBP may have contributed to the reduction in serum IGF-I by increasing IGF-I clearance from the circulation. Serum GH and prolactin were measured in samples obtained between 0900 and 1200 h. Serum GH did not differ with the exception of an increase on day 1 in control relative to RPL dams and on day 20 in RL dams relative to RPL and control. Serum prolactin was higher in the RL dams than controls on day 4. In summary, food restriction during pregnancy and lactation or solely during lactation results in similar reductions in serum IGF-I and alterations in serum IGFBP despite differences in body weight responses to food restriction during lactation. Journal of Endocrinology (1997) 152, 303–316

scholarly journals Basal and Growth Hormone-Induced Hepatic Messenger Ribonucleic Acid Expression of Insulin-Like Growth Factor-I (IGF-I) and IGF-Binding Protein-3 Is Independent of Hyperinsulinemia and Increased Energy Status in the Genetically Obese Zucker Rat*

Endocrinology ◽  
1997 ◽  
Vol 138 (3) ◽  
pp. 1066-1071 ◽  
Author(s):  
E. Melián ◽  
B. Velasco ◽  
R. Barrios ◽  
F. Sanchez-Franco
Keyword(s):  
Body Weight ◽  
Binding Protein ◽  
Zucker Rats ◽  
Energy Status ◽  
Igf I ◽  
Igf Binding ◽  
Obese Zucker Rats ◽  
Igf Binding Protein ◽  
Serum Gh ◽  
Igfbp 3

Abstract Genetically obese Zucker rats, like obese humans, have normal or elevated circulating insulin-like growth factor-I (IGF-I) levels in the presence of low GH secretion. Hyperinsulinemia, increased energy status, or other nutritional factors associated with obesity could be responsible for these findings directly by increasing hepatic IGF-I production at the transcriptional or posttranscriptional level. Alternatively, circulating IGF-I could be modulated indirectly by affecting its binding proteins. To further elucidate this point, we quantitated hepatic IGF-I, IGF binding protein-3 (IGFBP-3), and GH receptor messenger RNAs (mRNAs) expression in obese Zucker rats under different serum GH and insulin conditions using lean rats as controls. Eleven-week-old male rats were studied basally (intact) or after hypophysectomy (hx) at 9 weeks. In each condition, animals were killed before or 6 h after one dose of recombinant human GH (1.5 μg/g body weight ip). At this time, in addition to the mRNA expression of the above-mentioned genes, body weight, glycemia, insulinemia, serum GH (rat and human), and serum IGF-I levels were determined. Obese Zucker rats were significantly heavier than controls in all the conditions studied and did not show differences in glycemia. Severely hyperinsulinemic intact obese rats (146.9 ± 14 vs. 46.3 ± 3 μU/ml, P &lt; 0.001) showed compared with intact lean rats significantly lower serum GH (2.39 ± 0.9 vs. 4.98 ± 0.68 ng/ml, P &lt; 0.01), decreased hepatic IGF-I mRNA and IGFBP-3 mRNA accumulation (IGF-Ia: 79 ± 5.9% vs. 100 ± 0.9%, P &lt; 0.05; IGF-Ib: 67 ± 5.5% vs. 100.1 ± 1.9%,P &lt; 0.001; IGFBP-3: 54.7 ± 2.75% vs. 100.5 ± 1.55%, P &lt; 0.001), and similar circulating IGF-I levels (1439 ± 182 vs. 1516 ± 121 ng/ml). Under comparable serum GH levels in GH-treated intact, hx, and GH-treated hx animals, hyperinsulinemia and/or increased body weight present in obese rats were not associated with increased hepatic IGF-I and IGFBP-3 mRNA amount. No differences in GH receptor/GH-binding protein mRNAs were found in any experimental condition. These results suggest that in vivo the imbalance of the serum GH/IGF-I axis present in obesity is primarily due to events distal to the hepatic IGF-I and IGFBP-3 mRNAs expression, which is tightly correlated to GH levels.

scholarly journals Unequal impact of age, percentage body fat, and serum testosterone concentrations on the somatotrophic, IGF-I, and IGF-binding protein responses to a three-day intravenous growth hormone-releasing hormone pulsatile infusion in men

1998 ◽  
pp. 59-71 ◽  
Author(s):  
A Iranmanesh ◽  
S South ◽  
AY Liem ◽  
D Clemmons ◽  
MO Thorner ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Body Fat ◽  
Binding Protein ◽  
Serum Testosterone ◽  
Percentage Body Fat ◽  
Gh Secretion ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Serum Gh

We here investigate the potential rescue of the relative hyposomatotropism of aging and obesity by 3-day pulsatile GHRH infusions (i.v. bolus 0.33 microg/kg every 90 min) in 19 healthy men of varying ages (18 to 66 years) and body compositions (12 to 37% total body fat). Baseline (control) and GHRH-driven pulsatile GH secretion (in randomly ordered sessions) were quantitated by deconvolution analysis of 24-h (10-min sampling) serum GH concentration profiles measured in an ultrasensitive (threshold 0.005 microg/l) chemiluminescence assay. GHRH infusion significantly increased the mean (24-h) serum GH concentration (0.3 +/- 0.1 basal vs 2.4 +/- 0.4 microg/l treatment; P = 0.0001), total daily pulsatile GH production rate (21 +/- 9.5 vs 97 +/- 17 microg/l/day; P = 0.01), GH secretory burst frequency (11 +/- 0.5 vs 17 +/- 0.3 events/day; P = <0.01), and mass of GH released per burst (1.1 +/- 0.4 vs 5.9 1 microg/l; P < 0.01), as well as serum IGF-I (261 +/- 33 vs 436 +/- 37 microg/l; P = 0.005), insulin (45 +/- 13 vs 79 +/- 17 mU/l; P = 0.0002), and IGF binding protein (IGFBP)-3 (3320 +/- 107 vs 4320 +/- 114 microg/l; P = 0.001) concentrations, while decreasing IGFBP-1 levels (16 +/- 1.2 vs 14 +/- 0.09 microg/l; P = 0.02). Serum total testosterone and estradiol concentrations did not change. GHRH treatment also reduced the half-duration of GH secretory bursts, and increased the GH half-life. GHRH-stimulated 24-h serum GH concentrations and the mass of GH secreted per burst were correlated negatively with age (R[value]:P[value] = -0.67:0.002 and -0.58:0.009 respectively), and percentage body fat (R:P = -0.80:0.0001 and -0.65:0.0005 respectively), but positively with serum testosterone concentrations (R:P = +0.55:0.016 and +0.53:0.019 respectively). GHRH-stimulated plasma IGF-I increments correlated negatively with age and body mass index, and positively with serum testosterone, but not with percentage body fat. Cosinor analysis disclosed persistent nyctohemeral rhythmicity of GH secretory burst mass (with significantly increased 24-h amplitude and mesor values) but unchanged acrophase during fixed pulsatile GHRH infusions, which suggests that both GHRH- and non-GHRH-dependent mechanisms can modulate the magnitude (but only non-GHRH mechanisms can modulate the timing) of somatotrope secretory activity differentially over a 24-h period. In summary, diminished GHRH action and/or non-GHRH-dependent mechanisms (e.g. somatostatin excess, putative endogenous growth hormone-releasing peptide deficiency etc.) probably underlie the hyposomatotropism of aging, (relative) obesity, and/or hypoandrogenemia. Preserved or increased tissue IGF-I responses to GHRH-stimulated GH secretion (albeit absolutely reduced, suggesting GHRH insensitivity in obesity) may distinguish the pathophysiology of adiposity-associated hyposomatotropism from that of healthy aging.

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 MK-677, an Orally Active Growth Hormone Secretagogue, Reverses Diet-Induced Catabolism1

1998 ◽  
Vol 83 (2) ◽  
pp. 320-325 ◽  
Author(s):  
M. G. Murphy ◽  
L. M. Plunkett ◽  
B. J. Gertz ◽  
W. He ◽  
J. Wittreich ◽  
...  
Keyword(s):  
Placebo Group ◽  
Caloric Restriction ◽  
Nitrogen Balance ◽  
Binding Protein ◽  
Growth Hormone Secretagogue ◽  
Significant Difference ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Orally Active

The reversal of diet-induced negative nitrogen balance by GH suggests a possible therapeutic role for GH treatment in catabolic patients. A double-blind, randomized, placebo-controlled, two-period, cross-over study was designed to investigate whether MK-677, an orally active nonpeptide mimic of GH-releasing peptide, can reverse diet-induced protein catabolism. Eight healthy volunteers (ages 24–39 yr) were calorically restricted (18 kcal/kg·day) for two 14-day periods. During the last 7 days of each diet period, subjects received either oral MK-677 25 mg or placebo once daily. There was a 14- to 21-day washout interval between periods. During the first week of caloric restriction (i.e. diet alone), daily nitrogen losses were similar for both treatment groups (mean ± se; MK-677 group −2.67 ± 0.40 g/day vs. placebo group− 2.83 ± 0.26 g/day). During the second week (diet and study drug), mean daily nitrogen balance was 0.31 ± 0.21 g/day in the MK-677 treatment group compared with −1.48 ± 0.21 g/day in the placebo group (P &lt; 0.01). MK-677 improved nitrogen balance integrated over the 7 days of treatment; area under the curve day 8–14 nitrogen balance response was +2.69 ± 5.0 (se) for MK-677 and −8.97 ± 5.26 g·day for placebo (P &lt; 0.001). MK-677 produced a peak GH response of 55.9 ± 31.7 μg/L after single dose (day 1 of treatment) and 22.6 ± 9.3 μg/L after a week of dosing compared with placebo treatment peak GH values of approximately 9 (treatment day 1) and approximately 7 μg/L (treatment day 7). Following the initial 7-day caloric restriction, insulin-like growth factor-I (IGF-I) declined from 232 ± 25 to 186 ± 19 ng/mL in the MK-677 group and from 236 ± 19 to 174 ± 23 ng/mL in the placebo group. Mean IGF-I concentration increased significantly during MK-677 to 264 ± 31 ng/mL (mean for the last 5 days of treatment) compared with 188 ± 19 ng/mL with placebo (P &lt; 0.01). No significant difference in IGF binding protein-2 was found between the MK-677 and placebo treatments. However, the mean in IGF binding protein-3 for the last 5 days of MK-677 treatment was also significantly increased to 3273 ± 330 ng/mL (mean ± se) compared with placebo 2604 ± 253 ng/mL (P &lt; 0.01). Neither the serum cortisol nor the PRL response was significantly greater after 7 days of MK-677 dosing compared with 7 days of placebo. MK-677 (25 mg) was generally well tolerated and without clinically significant adverse experiences. In conclusion, MK-677 reverses diet-induced nitrogen wasting, suggesting that if these short-term anabolic effects are maintained in patients who are catabolic because of certain acute or chronic disease states, it may be useful in treating catabolic conditions.

scholarly journals Genetic Determinants of Circulating Insulin-Like Growth Factor (IGF)-I, IGF Binding Protein (BP)-1, and IGFBP-3 Levels in a Multiethnic Population

2007 ◽  
Vol 92 (9) ◽  
pp. 3660-3666 ◽  
Author(s):  
Iona Cheng ◽  
Katherine DeLellis Henderson ◽  
Christopher A. Haiman ◽  
Laurence N. Kolonel ◽  
Brian E. Henderson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Genetic Determinants ◽  
Igf I ◽  
Igf Binding ◽  
Multiethnic Population ◽  
Igf Binding Protein ◽  
Igfbp 3
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