Tissue-specific alterations in insulin-like growth factor-I concentrations in response to 3,3',5-triiodo-L-thyronine supplementation in the growth hormone receptor-deficient sex-linked dwarf chicken

Regina Vasilatos-Younken, E. A. Dunnington, P. B. Siegel, J. P. McMurtry

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Abstract

Insulin-like growth factor-I (IGF-I) mediates many of the effects of growth hormone (GH). The regulation of IGF-I, independent of GH, is methodologically difficult to assess in vivo, as hypophysectomy results in derangement of many pituitary hormone axes in addition to GH, and a gene knockout model is not available. The recessive sex-linked dwarfing (SLD) gene (dw) in chickens results in a lack of functional target tissue GH receptors due to a variety of molecular defects, which provides a unique model for evaluating GH-independent regulation of IGF-I. In the present study, the impact of 3,3',5-triiodo-L-thyronine (T3) on circulating and tissue IGF-I was determined in normal versus SLD birds. Adult, nonovulatory female normal and SLD chickens were restrict-fed 40 g of feed/kg bw/day containing 0, 0.5, or 1.0 ppm T3, resulting in supplementation levels of 0 (control), 20 (low dose), or 40 (high dose) μg T3/kg bw/day for 10 days. Samples of GH target tissues including liver, abdominal fat pad, skeletal muscle (pectoralis major), and spleen were extracted and assayed for IGF-I. Plasma T3, T4, GH, and IGF-I were determined by homologous RIA. Tissue GH binding was determined for hepatic membranes by radioreceptor assay. Under control conditions, dwarf chickens were markedly hypersomatotropic (33.3 ± 4.1 ng GH/ml plasma; mean ± SEM) compared to normals (2.4 ± 3.9 ng/ml), and T3 supplementation reduced this to normal levels. Despite the high circulating level of GH in dwarfs, plasma IGF-I was low compared to normal controls (dwarfs 1.5 ± .9 ng/ml normals 5.3 ± .9 ng/ml; P = 0.004), but this difference was eliminated with low-dose T3. In this study, tissue IGF-I was undetectable in liver and pectoralis muscle in adults (55 weeks of age) of both genotypes, under all treatments. In contrast, adipose tissue IGF-I was relatively high and did not differ (P = 0.84) between genotypes under control conditions (normals 776.5 ± 236.7 dwarfs 844.6 ± 236.7 pg/mg protein), but was increased in normals and decreased in dwarfs, resulting in higher levels (P = 0.02) in the normal (1249.9 ± 200.0 pg/mg protein) than in the dwarf genotype (558.4 ± 200.0 pg/mg protein) at the higher level of T3 supplementation. This relationship was somewhat reversed in spleen where T3 tended to decrease tissue IGF-I concentration in normals and increase it in dwarfs. The low level of plasma IGF-I despite nonmeasurable hepatic IGF-I tissue concentrations suggests that IGF-I synthesis by extrahepatic tissues contributes to the circulating pool of IGF-I. The relatively high control levels of adipose tissue IGF-I in the dwarf genotype further suggest that considerable IGF-I synthesis exists that is GH-independent in this extrahepatic tissue. The presence of GH action, however, may mediate the effects of other hormones that can influence local IGF-I production in this tissue, as reflected by the differential response to T3 supplementation between genotypes. The tissue-specific nature of the effect of T3 on IGF-I production supports an additional point of regulation of hormone action at the target tissue level.

Original languageEnglish (US)
Pages (from-to)31-39
Number of pages9
JournalGeneral and Comparative Endocrinology
Volume105
Issue number1
DOIs
StatePublished - Jan 1 1997

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thyronine
Thyronines
Somatotropin Receptors
insulin-like growth factor I
Insulin-Like Growth Factor I
Chickens
chickens
triiodothyronine
gender
somatotropin
Growth Hormone
Genotype
dwarfing
genotype
somatotropin receptors
tissues
Adipose Tissue
liver
Liver
adipose tissue

All Science Journal Classification (ASJC) codes

  • Animal Science and Zoology
  • Endocrinology

Cite this

@article{43e74df01cb14a419063c575ed6ae44e,
title = "Tissue-specific alterations in insulin-like growth factor-I concentrations in response to 3,3',5-triiodo-L-thyronine supplementation in the growth hormone receptor-deficient sex-linked dwarf chicken",
abstract = "Insulin-like growth factor-I (IGF-I) mediates many of the effects of growth hormone (GH). The regulation of IGF-I, independent of GH, is methodologically difficult to assess in vivo, as hypophysectomy results in derangement of many pituitary hormone axes in addition to GH, and a gene knockout model is not available. The recessive sex-linked dwarfing (SLD) gene (dw) in chickens results in a lack of functional target tissue GH receptors due to a variety of molecular defects, which provides a unique model for evaluating GH-independent regulation of IGF-I. In the present study, the impact of 3,3',5-triiodo-L-thyronine (T3) on circulating and tissue IGF-I was determined in normal versus SLD birds. Adult, nonovulatory female normal and SLD chickens were restrict-fed 40 g of feed/kg bw/day containing 0, 0.5, or 1.0 ppm T3, resulting in supplementation levels of 0 (control), 20 (low dose), or 40 (high dose) μg T3/kg bw/day for 10 days. Samples of GH target tissues including liver, abdominal fat pad, skeletal muscle (pectoralis major), and spleen were extracted and assayed for IGF-I. Plasma T3, T4, GH, and IGF-I were determined by homologous RIA. Tissue GH binding was determined for hepatic membranes by radioreceptor assay. Under control conditions, dwarf chickens were markedly hypersomatotropic (33.3 ± 4.1 ng GH/ml plasma; mean ± SEM) compared to normals (2.4 ± 3.9 ng/ml), and T3 supplementation reduced this to normal levels. Despite the high circulating level of GH in dwarfs, plasma IGF-I was low compared to normal controls (dwarfs 1.5 ± .9 ng/ml normals 5.3 ± .9 ng/ml; P = 0.004), but this difference was eliminated with low-dose T3. In this study, tissue IGF-I was undetectable in liver and pectoralis muscle in adults (55 weeks of age) of both genotypes, under all treatments. In contrast, adipose tissue IGF-I was relatively high and did not differ (P = 0.84) between genotypes under control conditions (normals 776.5 ± 236.7 dwarfs 844.6 ± 236.7 pg/mg protein), but was increased in normals and decreased in dwarfs, resulting in higher levels (P = 0.02) in the normal (1249.9 ± 200.0 pg/mg protein) than in the dwarf genotype (558.4 ± 200.0 pg/mg protein) at the higher level of T3 supplementation. This relationship was somewhat reversed in spleen where T3 tended to decrease tissue IGF-I concentration in normals and increase it in dwarfs. The low level of plasma IGF-I despite nonmeasurable hepatic IGF-I tissue concentrations suggests that IGF-I synthesis by extrahepatic tissues contributes to the circulating pool of IGF-I. The relatively high control levels of adipose tissue IGF-I in the dwarf genotype further suggest that considerable IGF-I synthesis exists that is GH-independent in this extrahepatic tissue. The presence of GH action, however, may mediate the effects of other hormones that can influence local IGF-I production in this tissue, as reflected by the differential response to T3 supplementation between genotypes. The tissue-specific nature of the effect of T3 on IGF-I production supports an additional point of regulation of hormone action at the target tissue level.",
author = "Regina Vasilatos-Younken and Dunnington, {E. A.} and Siegel, {P. B.} and McMurtry, {J. P.}",
year = "1997",
month = "1",
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doi = "10.1006/gcen.1996.6795",
language = "English (US)",
volume = "105",
pages = "31--39",
journal = "General and Comparative Endocrinology",
issn = "0016-6480",
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T1 - Tissue-specific alterations in insulin-like growth factor-I concentrations in response to 3,3',5-triiodo-L-thyronine supplementation in the growth hormone receptor-deficient sex-linked dwarf chicken

AU - Vasilatos-Younken, Regina

AU - Dunnington, E. A.

AU - Siegel, P. B.

AU - McMurtry, J. P.

PY - 1997/1/1

Y1 - 1997/1/1

N2 - Insulin-like growth factor-I (IGF-I) mediates many of the effects of growth hormone (GH). The regulation of IGF-I, independent of GH, is methodologically difficult to assess in vivo, as hypophysectomy results in derangement of many pituitary hormone axes in addition to GH, and a gene knockout model is not available. The recessive sex-linked dwarfing (SLD) gene (dw) in chickens results in a lack of functional target tissue GH receptors due to a variety of molecular defects, which provides a unique model for evaluating GH-independent regulation of IGF-I. In the present study, the impact of 3,3',5-triiodo-L-thyronine (T3) on circulating and tissue IGF-I was determined in normal versus SLD birds. Adult, nonovulatory female normal and SLD chickens were restrict-fed 40 g of feed/kg bw/day containing 0, 0.5, or 1.0 ppm T3, resulting in supplementation levels of 0 (control), 20 (low dose), or 40 (high dose) μg T3/kg bw/day for 10 days. Samples of GH target tissues including liver, abdominal fat pad, skeletal muscle (pectoralis major), and spleen were extracted and assayed for IGF-I. Plasma T3, T4, GH, and IGF-I were determined by homologous RIA. Tissue GH binding was determined for hepatic membranes by radioreceptor assay. Under control conditions, dwarf chickens were markedly hypersomatotropic (33.3 ± 4.1 ng GH/ml plasma; mean ± SEM) compared to normals (2.4 ± 3.9 ng/ml), and T3 supplementation reduced this to normal levels. Despite the high circulating level of GH in dwarfs, plasma IGF-I was low compared to normal controls (dwarfs 1.5 ± .9 ng/ml normals 5.3 ± .9 ng/ml; P = 0.004), but this difference was eliminated with low-dose T3. In this study, tissue IGF-I was undetectable in liver and pectoralis muscle in adults (55 weeks of age) of both genotypes, under all treatments. In contrast, adipose tissue IGF-I was relatively high and did not differ (P = 0.84) between genotypes under control conditions (normals 776.5 ± 236.7 dwarfs 844.6 ± 236.7 pg/mg protein), but was increased in normals and decreased in dwarfs, resulting in higher levels (P = 0.02) in the normal (1249.9 ± 200.0 pg/mg protein) than in the dwarf genotype (558.4 ± 200.0 pg/mg protein) at the higher level of T3 supplementation. This relationship was somewhat reversed in spleen where T3 tended to decrease tissue IGF-I concentration in normals and increase it in dwarfs. The low level of plasma IGF-I despite nonmeasurable hepatic IGF-I tissue concentrations suggests that IGF-I synthesis by extrahepatic tissues contributes to the circulating pool of IGF-I. The relatively high control levels of adipose tissue IGF-I in the dwarf genotype further suggest that considerable IGF-I synthesis exists that is GH-independent in this extrahepatic tissue. The presence of GH action, however, may mediate the effects of other hormones that can influence local IGF-I production in this tissue, as reflected by the differential response to T3 supplementation between genotypes. The tissue-specific nature of the effect of T3 on IGF-I production supports an additional point of regulation of hormone action at the target tissue level.

AB - Insulin-like growth factor-I (IGF-I) mediates many of the effects of growth hormone (GH). The regulation of IGF-I, independent of GH, is methodologically difficult to assess in vivo, as hypophysectomy results in derangement of many pituitary hormone axes in addition to GH, and a gene knockout model is not available. The recessive sex-linked dwarfing (SLD) gene (dw) in chickens results in a lack of functional target tissue GH receptors due to a variety of molecular defects, which provides a unique model for evaluating GH-independent regulation of IGF-I. In the present study, the impact of 3,3',5-triiodo-L-thyronine (T3) on circulating and tissue IGF-I was determined in normal versus SLD birds. Adult, nonovulatory female normal and SLD chickens were restrict-fed 40 g of feed/kg bw/day containing 0, 0.5, or 1.0 ppm T3, resulting in supplementation levels of 0 (control), 20 (low dose), or 40 (high dose) μg T3/kg bw/day for 10 days. Samples of GH target tissues including liver, abdominal fat pad, skeletal muscle (pectoralis major), and spleen were extracted and assayed for IGF-I. Plasma T3, T4, GH, and IGF-I were determined by homologous RIA. Tissue GH binding was determined for hepatic membranes by radioreceptor assay. Under control conditions, dwarf chickens were markedly hypersomatotropic (33.3 ± 4.1 ng GH/ml plasma; mean ± SEM) compared to normals (2.4 ± 3.9 ng/ml), and T3 supplementation reduced this to normal levels. Despite the high circulating level of GH in dwarfs, plasma IGF-I was low compared to normal controls (dwarfs 1.5 ± .9 ng/ml normals 5.3 ± .9 ng/ml; P = 0.004), but this difference was eliminated with low-dose T3. In this study, tissue IGF-I was undetectable in liver and pectoralis muscle in adults (55 weeks of age) of both genotypes, under all treatments. In contrast, adipose tissue IGF-I was relatively high and did not differ (P = 0.84) between genotypes under control conditions (normals 776.5 ± 236.7 dwarfs 844.6 ± 236.7 pg/mg protein), but was increased in normals and decreased in dwarfs, resulting in higher levels (P = 0.02) in the normal (1249.9 ± 200.0 pg/mg protein) than in the dwarf genotype (558.4 ± 200.0 pg/mg protein) at the higher level of T3 supplementation. This relationship was somewhat reversed in spleen where T3 tended to decrease tissue IGF-I concentration in normals and increase it in dwarfs. The low level of plasma IGF-I despite nonmeasurable hepatic IGF-I tissue concentrations suggests that IGF-I synthesis by extrahepatic tissues contributes to the circulating pool of IGF-I. The relatively high control levels of adipose tissue IGF-I in the dwarf genotype further suggest that considerable IGF-I synthesis exists that is GH-independent in this extrahepatic tissue. The presence of GH action, however, may mediate the effects of other hormones that can influence local IGF-I production in this tissue, as reflected by the differential response to T3 supplementation between genotypes. The tissue-specific nature of the effect of T3 on IGF-I production supports an additional point of regulation of hormone action at the target tissue level.

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