ABSTRACT
112Thyroid hormone (T3) stimulates energy turnover in mammals in the resting situation but also in the activated state. The increased energy cost to deliver a given amount of work leads to lowered mechanical efficiency of muscle contraction in hyperthyroidism and vice versa in hypothyroidism. In return for the lowered mechanical efficiency which is caused by T3, the speed of contraction and relaxation increases. These mechanical changes reflect increases in Actomyosin-ATPase and Ca-ATPase activity. The increase in tension-dependent (crossbridge cycling) and -independent (Ca cycling) heat production is in line with these observations. At the molecular level these T3-induced effects correspond with a slow to fast isoform shift in the expression of the myosin heavy chain and in the case of Ca-ATPase by an increase of both fast (in slow and fast muscle) and slow isoform (in slow muscle) units. The effects of T3 on energy turnover and contractility are generally larger in slow muscle than in fast muscle because in fast muscle T3-stimulated protein isoforms of actomyosin-ATPase and Ca-ATPase are already largely expressed in the absence of T3, which limits the range of regulation. The T3-induced increase in energy requirement during contraction is accompanied by an increased capacity for mitochondrial respiration (slow muscle) and glyco(geno)lysis (fast muscle). Changes in the level of Phosphorylase kinase (PpK) (100%) are largely responsible for the altered glyco(geno)lytic energy fluxes in different thyroid states. It was shown that there was a positive correlation between PpK levels, Phosphorylase activation, and lactate production in fast muscles of different thyroid states. It is concluded that T3 transforms a phenotypically slow muscle into a fast muscle by a coordinated regulation of key proteins that are involved in the contraction-relaxation process and in the supply of ATP. The overall effect is increased contractility at a higher energy turnover rate. The T3- induced ATP turnover stimulation in combination with the stimulation of Ca2+ -transport has dualistic effects on the recovery process in energy depleted heart tissue. ATP depletion proceeds slower in hypothyroid heart than in the cytosolic T3-treated heart during metabolic inhibition, thereby delaying the time onset of the harmful Ca2+ rise. However, once beyond the point of ATP depletion in the rigor phase, when Ca2+ rises, the T3-treated heart in contrast to the hypothyroid heart is better equipped to normalize Ca homeostasis in the recovery phase owing to its higher capacity for ATP production and Ca removal.
