Age-related alterations in the response of hepatic lipogenic enzymes to altered thyroid states in the rat

Abstract

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 α-glycerophosphate dehydrogenase (α-GPD) were determined in groups of euthyroid, hypothyroid and hyperthyroid male Fischer 344 rats at various ages. The basal α-GPD level (change in optical density/min per mg) in 2-month-old rats (0·163 ±0·003) (s.e.m.) was significantly (P < 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 < 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 α-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. Journal of Endocrinology (1991) 128, 79–84