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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.
Gen Comp Endocrinol. 1997 Jan; 105(1):31-9.GC

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) microg 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 nonmeasureable 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.

Authors+Show Affiliations

Department of Poultry Science, Pennsylvania State University, University Park, Pennsylvania, 16802, USA. rxv@psuvm.psu.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9000465

Citation

Vasilatos-Younken, R, et al. "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." General and Comparative Endocrinology, vol. 105, no. 1, 1997, pp. 31-9.
Vasilatos-Younken R, Dunnington EA, Siegel PB, et al. 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. Gen Comp Endocrinol. 1997;105(1):31-9.
Vasilatos-Younken, R., Dunnington, E. A., Siegel, P. B., & McMurtry, J. P. (1997). 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. General and Comparative Endocrinology, 105(1), 31-9.
Vasilatos-Younken R, et al. 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. Gen Comp Endocrinol. 1997;105(1):31-9. PubMed PMID: 9000465.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR 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,R, AU - Dunnington,E A, AU - Siegel,P B, AU - McMurtry,J P, PY - 1997/1/1/pubmed PY - 1997/1/1/medline PY - 1997/1/1/entrez SP - 31 EP - 9 JF - General and comparative endocrinology JO - Gen. Comp. Endocrinol. VL - 105 IS - 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) microg 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 nonmeasureable 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. SN - 0016-6480 UR - https://www.unboundmedicine.com/medline/citation/9000465/Tissue_specific_alterations_in_insulin_like_growth_factor_I_concentrations_in_response_to_33'5_triiodo_L_thyronine_supplementation_in_the_growth_hormone_receptor_deficient_sex_linked_dwarf_chicken_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-6480(96)96795-7 DB - PRIME DP - Unbound Medicine ER -