Factors Determining the Level of Activity of 3,5,3- Triiodothyronine-Responsive Hepatic Enzymes in the Starved Rat*

Publisher Website
Google Scholar
Abstract
Recent studies have indicated that starvation can cause profound alterations in components of the thyroid hormone system. A systematic study was therefore undertaken to assess the effect of these changes on the rate of appearance oftwo thyroid hormone-responsive hepatic enzymes, mitochondrial α-glycerophosphate dehydrogenase (α-GPD) and cytosolic malic enzyme (ME). The fractional rates of disappearance of enzyme activity, in both the fed and starved state, were determined after pretreatment with T3. An almost 2-fold increase in the fractional disappearance rate was noted for both enzymes during starvation (ME, 0.22 vs. 0.43 day-1; α-GPD, 0.18 vs. 0.32 day-1). Knowledge of these values together with measurements of the enzyme activity per mg DNA in uninjected rats allowed calculation of the simultaneous rates of appearance and disappearance of enzyme activity during the 5-day starvation period. During the first 3 days, the rate of appearance of α-GPD was preserved at near-normal values (89% of fed baseline), whereas the rate of formation of ME was severely reduced (19% of fed baseline). During the last 2 days of starvation, the rate of formation of both enzymes was estimated to be near zero. The preferential maintenance of the α-GPD appearance rate during the first 3 days of starvation was of interest in view of the reduction in the T3 nuclear content during this period to one third of the normal fed value. This pointed to the importance of postreceptor factorsin augmenting the signal generated by the T3-nuclear receptornteraction. In the case of ME, the specific appearance rate, alculated as the rate of enzyme generation per ng nuclear T3, was reduced to 29% of the basal fed state during the first 3 days of starvation. Thus, the signal from the T3-nuclear complex wasinhibited. The importance of starvation-related postreceptor factors in augmenting α-GPD and inhibiting ME response was so illustrated in experiments in which the rate of formation of the enzymes was estimated in starved and fed animals treated with large doses of T3 designed to saturate the nuclear refectories. Our results, therefore, emphasize the importance of local cellular factors in inhibiting or augmenting the response to a given concentration of the T3-nuclear complex. Furthermore, the suppression of ME formation may be a reflection of thenecessity for reduced lipogenesis in starvation. The tendency to aintain α-GPD suggests an important role for this enzyme during starvation.