Altered chicken thyroid hormone metabolism with chronic GH enhancement in vivo: consequences for skeletal muscle growth.
In contrast to most vertebrates, GH reportedly has no effect upon somatic growth of the chicken. However, previous studies employed only one to two dosages of the hormone, and limited evidence exists of a hyperthyroid response that may confound its anabolic potential. This study evaluated the effects of 0, 10, 50, 100 and 200 microgram/kg body weight per day chicken GH (cGH) (0-200 GH) infused i.v. for 7 days in a pulsatile pattern to immature, growing broiler chickens (9-10 birds/dosage). Comprehensive profiles of thyroid hormone metabolism and measures of somatic growth were obtained. Overall (average) body weight gain was reduced 25% by GH, with a curvilinear, dose-dependent decrease in skeletal (breast) muscle mass that was maximal (12%) at 100 GH. This profile mirrored GH dose-dependent decreases in hepatic type III deiodinase (DIII) activity and increases in plasma tri-iodothyronine (T(3)), with bot! h also maximal (74 and 108% respectively) at 100 GH. No effect on type I deiodinase was observed. At the maximally effective dosage, hepatic DIII gene expression was reduced 44% versus controls. Despite dose-dependent, fold-increases in hepatic IGF-I protein content, circulating IGF-I was not altered with GH infusion, suggesting impairment of hepatic IGF-I release. Significant, GH dose-dependent increases in plasma non-esterified fatty acid and glucose, and overall decreases in triacylglycerides were also observed. At 200 GH, feed intake was significantly reduced (19%; P<0.05) versus controls; however, additional control birds pair-fed to this level did not exhibit any responses observed for GH-treated birds. The results of this study support a pathway by which GH impacts on thyroid hormone metabolism beginning at a pretranslational level, with reduced hepatic DIII gene expression, translating to reduced protein (enzyme) ex! pression, and reflected in a reduced level of peripheral T(3)-degrading activity. This contributes to decreased conversion of T(3) to its inactive form, thereby elevating circulating T(3) levels. The hyper-T(3) state leads to reduced net skeletal muscle deposition, and may impair release of GH-enhanced, hepatic IGF-I. In conclusion, GH has significant biological effects in the chicken, but profound metabolic actions predominate that may confound positive, IGF-I-mediated skeletal muscle growth.
Vasilatos-Younken
R
R
Department of Poultry Science, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Zhou
Y
Y
Wang
X
X
McMurtry
J P
JP
Rosebrough
R W
RW
Decuypere
E
E
Buys
N
N
Darras
V M
VM
Van Der Geyten
S
S
Tomas
F
F
D000273:Adipose Tissue / Q000033:anatomy & histology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015152:Blotting, Northern; D001835:Body Weight / Q000187:drug effects; D002645:Chickens / Q000097:blood / Q000254:growth & development*; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D013006:Growth Hormone / Q000008:administration & dosage* / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000033:anatomy & histology; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism; D008762:Methylhistidines / Q000378:metabolism; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000254:growth & development*; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D012044:Regression Analysis; D013154:Spleen / Q000033:anatomy & histology; D013963:Thyroid Hormones / Q000097:blood*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D008762:Methylhistidines; D012333:RNA, Messenger; D013963:Thyroid Hormones; D014284:Triiodothyronine; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D007453:Iodide Peroxidase; C028118:3-methylhistidine; D013974:Thyroxine