Is altered expression of hepatic insulin-related genes in growth hormone receptor knockout mice due to GH resistance or a difference in biological life spans?
Growth hormone receptor knockout (GHRKO) mice live about 40%-55% longer than their normal (N) littermates. Previous studies of 21-month-old GHRKO and N mice showed major alterations of the hepatic expression of genes involved in insulin signaling. Differences detected at this age may have been caused by the knockout of the growth hormone receptor (GHR) or by differences in biological age between GHRKO and N mice. To address this question, we compared GHRKO and N mice at ages corresponding to the same percentage of median life span to see if the differences of gene expression persisted. Comparison of GHRKO and N mice at approximately 50% of biological life span showed significant differences in hepatic expression of all 14 analyzed genes. We conclude that these changes are due to disruption of GHR gene and the consequent suppression of growth hormone signaling rather than to differences in "biological age" between mutant and normal animals sampled at the same chronological age.
Panici
Jacob A
JA
Department of Internal Medicine, Geriatrics Research, Springfield, IL 62794-9628, USA.
Wang
Feiya
F
Bonkowski
Michael S
MS
Spong
Adam
A
Bartke
Andrzej
A
Pawlikowska
Ludmila
L
Kwok
Pui-Yan
PY
Masternak
Michal M
MM
D000818:Animals; D005838:Genotype; D013006:Growth Hormone / Q000502:physiology*; D007328:Insulin / Q000097:blood / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008136:Longevity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000032:analysis; D011986:Receptors, Somatotropin / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors
D007328:Insulin; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D015534:Trans-Activators; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone
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