Effects of physiological levels of thyroxine in vivo on respiration and phosphorylation in rat liver fractions

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Abstract
Liver mitochondrial systems of varying heterogeneity with respect to microsomal-soluble components were isolated from thyroidectomized and normal rats given l-thyroxine at various dose levels (0, 3, 10, 30, 100, 500 and > 500 µg daily) for 14 days. Degree of homogeneity of fractions was checked by electron and light microscopy. Determinations were made as functions of fraction and thyroxine dose on respiration, phosphorylation, TPNH- and DPNH-cytochrome c reductase activities, DPN content and optical densities. With well washed, homogeneous mitochondrial preparations, stimulation of respiration was obtained without concurrent reduction in P/O ratios, whereas in the more heterogeneous fractions, the qO2OO2 was not elevated, and P/O ratios decreased with increasing dose levels. DPNH- and TPNH-cytochrome c reductase levels were respectively decreased and increased with increasing hormone dosages; the extent of mitochondrial swelling increased, and the DPN content of the mitochondria decreased with dose. The striking change effected by thyroxine on the cytochrome c reductases is at variance with current theory on the regulatory role assigned to the TPNH-DPNH shunt in this respect. Results indicate that thyroxine controls respiration in the mitochondrion directly but that this agent may exert its effects on the phosphorylating activities of the cell by action primarily at some extramitochondrial site.