Age-related alterations in the response of hepatic lipogenic enzymes to altered thyroid states in the rat.
To determine the age-related alterations in tissue-responsiveness to thyroid hormone action, the mRNA levels and the enzyme activities of hepatic cytosolic malate dehydrogenase (ME) and mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) were determined in groups of euthyroid, hypothyroid and hyperthyroid male Fischer 344 rats at various ages. The basal alpha-GPD level (change in optical density/min per mg) in 2-month-old rats (0.163 +/- 0.003) (S.E.M.) was significantly (P less than 0.001) higher than that in 6-month-old and 26-month-old rats (0.116 +/- 0.012 and 0.098 +/- 0.013 respectively). The basal ME activity (mU/mg) was significantly (P less than 0.001) reduced in aged rats (9.2 +/- 0.89) compared with younger rats (54.2 +/- 3.4 and 17.1 +/- 2.3 for 2-month-old and 6-month-old rats respectively). The response of ME to tri-iodothyronine (T3) in aged rats compared with young rats was reduced approximately 50%. This age-related reduction in ME response to T3 could not be attributed to reduced food intake with ageing. Northern blot analysis showed that ME mRNA levels in hyperthyroid aged rats were 50% of those of young hyperthyroid rats. There were no significant differences in either basal or T3-stimulated alpha-GPD mRNA levels. The proportional reduction in steady-state ME mRNA levels and ME activity in aged rats indicates that this age-related change is modulated at a pretranslational level.
Mooradian
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AD
Division of Restorative Medicine, University of Arizona, Tucson 85719.
Deebaj
L
L
Wong
N C
NC
D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D015152:Blotting, Northern; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008291:Malate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013961:Thyroid Gland / Q000378:metabolism*; D013963:Thyroid Hormones / Q000502:physiology*; D014284:Triiodothyronine / Q000494:pharmacology
D012333:RNA, Messenger; D013963:Thyroid Hormones; D014284:Triiodothyronine; D005993:Glycerolphosphate Dehydrogenase; D008291:Malate Dehydrogenase