Thyroid hormones control lysosomal enzyme activities in liver and skeletal muscle

Abstract

Because protein degradation in liver and skeletal muscle is increased by thyroid hormones and decreased by thyroidectomy, we investigated the influence of thyroid hormones on the level of lysosomal enzymes. Hypophysectomized rats received daily injections of L-thyroxine or L-triiodothyronine. After 3 days of this regimen, homogenates of liver and skeletal muscle showed a 2-to 3-fold increase in the activities of cathepsin D, cathepsin B, and other lysosomal enzymes including leucine aminopeptidase, acid phosphatase, i3-galactosidase, N-acetylglucosaminidase, and a-mannosidase.In liver, this effect reflected increased enzyme activity in the two subcellular fractions that normally contain lysosomes. Titration of cathepsin D with pepstatin indicated that the increase in this activity resulted from an increase in the number of enzyme molecules. These effects occurred with both pharmacologic (thyrotoxic) and physiologic (growth-promoting) doses of thyroid hormones. Liver and skeletal muscle from thyroidectomized rats had approximately 50% of the normal levels of lysosomal enzyme activities. Under these various conditions, heart and kidney, tissues in which protein degradation does not appear to be influenced by thyroid hormones, showed no significant changes in lysosomal hydrolases. Thus, thyroid hormones regulate proteolytic and other lysosomal enzyme activities in those tissues in which these hormones influence protein degradation. Many characteristic features of hyperthyroidism and hypothyroidism may result from changes in levels of lysosomal enzymes.In mammalian cells, several hormones are known to regulate the average rates of protein degradation (1, 2). For example, in liver, insulin decreases overall proteolysis (3, 4) whereas glucagon stimulates this process (5, 6), and these effects are important in regulating protein content of this organ (2). Recent studies (7,8) in this laboratory demonstrated that thyroid hormones also have important effects on average rates of protein degradation in addition to other known effects in promoting protein synthesis. Thyroidectomy or hypophysectomy, either of which greatly diminishes thyroid hormone production, decreased protein degradation in skeletal muscles of rats. Physiologic doses of thyroxine (T4) or triiodothyronine (T3) induced muscle growth and increased both protein synthesis and protein degradation. Higher doses of these hormones increased protein degradation further but did not change protein synthesis rates beyond those observed with growth-promoting doses. Thus, the severe muscle wasting observed in hyperthyroidism appears to result from increased protein degradation. In addition, thyroid hormones were found to increase protein degradation in liver but not in heart or kidney (7). The present studies were undertaken to clarify the mechanism by which thyroid hormones influence protein catabolism.Mammalian tissues contain both lysosomal and nonlysosomal proteases (2). Although certain proteins (e.g., proteins with abnormal conformations) appear to be degr...

Renal proteinases and kidney hypertrophy in experimental diabetes

“…While we do not have direct experimental evidence, several observations suggest a close relationship. Inhibition of lysosomal cathepsins may reduce intracellular protein breakdown by up to 70 % [24][25][26], whereas protein degradation has been shown to be paralleled by enhanced cathepsin activity [27][28][29][30]. These findings support the view that lysosomal proteinases are related to intracellular protein turnover, such that reduced activity would favour protein accumulation.…”

Serum hexosaminidase and ß-glucuronidase activities in infants: effects of age and sex

“…In an attempt to elucidate this last aspect, Tenore et al (15) found a positive correlation between the changes of serum HEX and thyroxin levels in newborns. The potential role of thyroxin in HEX activity has been formerly suggested by the finding of approximately 50% of the normal HEX level in skeletal muscle and liver of thyroidectomized rats (19). A positive correlation between thyroxin level and serum HEX activity has been reported in euthyroid, hypothyroid and hyperthyroid prepuberal females (20), suggesting the influence of this hormone on human HEX activity as well.…”

Influence of hyperthyroidism on splanchnic exchange of glucose and gluconeogenic precursors.

“…The metabolic effects of hyperthyroidism have been well characterized with respect to increased oxygen consumption (1,2), augmented adipose tissue lipolysis (3,4), and net protein catabolism (5,6). The effects of hyperthyroidism on hepatic gluconeogenesis have been less clearly established.…”