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.
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.
Vasilatos-Younken
R
R
Department of Poultry Science, Pennsylvania State University, University Park, Pennsylvania, 16802, USA. rxv@psuvm.psu.edu
Dunnington
E A
EA
Siegel
P B
PB
McMurtry
J P
JP
D000273:Adipose Tissue / Q000737:chemistry* / Q000187:drug effects; D000818:Animals; D002645:Chickens / Q000097:blood / Q000502:physiology*; D004195:Disease Models, Animal; D004392:Dwarfism / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D008040:Genetic Linkage; D013006:Growth Hormone / Q000097:blood / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000187:drug effects; D011986:Receptors, Somatotropin / Q000172:deficiency* / Q000235:genetics; D013154:Spleen / Q000737:chemistry / Q000187:drug effects; D013974:Thyroxine / Q000097:blood / Q000187:drug effects; D014284:Triiodothyronine / Q000097:blood / Q000187:drug effects / Q000494:pharmacology*; D014960:X Chromosome
D011986:Receptors, Somatotropin; D014284:Triiodothyronine; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013974:Thyroxine