Role of the pituitary and thyroid glands in the decline of minimal O2 consumption with age.

Denckla, W D

doi:10.1172/jci107592

Cited by 105 publications

(39 citation statements)

References 25 publications

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“…Although several age-related changes have been re ported to be thyroid hormone dependent [4,7], this report implicates the central nervous system in this regard. Numer ous studies have shown that the central nervous system is markedly dependent on thyroid hormones for its overall growth and its morphological and biochemical develop ment [5,14).…”

Section: Discussionmentioning

confidence: 53%

“…With increasing age, in the rat there is a thyroid hormone-dependent decline in mini mal oxygen consumption (MOC) [4], and studies in humans show a decline in thyroxine (T4) secretion [7] and the abso lute rate of thyroid iodine accumulation [8], Data also sug gests an age-related insensitivity to thyroid hormone at the tissue level [4,11] and a thyroid hormone-dependent decline in rat renal cortical Na*-K+ ATPase [11]. Much work has been done to evaluate serum T3 concentrations in respect to increasing age [12,15,22).…”

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confidence: 99%

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Interaction of Age and Thyroid Hormone Status on Beta-Endorphin Content in Rat Corpus Striatum and Hypothalamus

Gambert¹

1981

Neuroendocrinology

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These studies investigated the effect of aging on thyroid hormone regulation of β-endorphin in rat corpus striatum and hypothalamus. In both brain areas, basal levels of β-endorphin declined with age. In addition, age modified the response of β-endorphin to thyroid hormone status. Hypothyroid rats aged 6 months (mature) exhibited a 67% mean decline in the level of β-endorphin in the corpus striatum. Hypothyroid rats aged 20–24 months (senescent) exhibited no change in the level of β-endorphin in the corpus striatum. Hypothyroid rats aged 6 months had a 28% mean decline in the level of hypothalamic β-endorphin. There was no change in hypothalamic β-endorphin content in hypothyroid senescent rats. Hyperthyroidism resulted in elevations of β-endorphin in both the corpus striatum and hypothalamus in senescent, but not mature rats. Changes in β-endorphin seen with age are at least in part thyroid hormone dependent. In addition, age is capable of modifying the response of brain tissue to thyroid hormone.

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Section: Discussionmentioning

confidence: 53%

mentioning

confidence: 99%

Interaction of Age and Thyroid Hormone Status on Beta-Endorphin Content in Rat Corpus Striatum and Hypothalamus

Gambert¹

1981

Neuroendocrinology

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“…Similar increases in lysosomal enzyme activities also occurred when physiologic doses of T3 (2 jg/100 g body wt per day) were injected into hypophysectomized rats (Table 4). This dose caused a small but significant increase in body weight and should be equivalent to the amount normally produced by rats of this size (23).…”

Section: Resultsmentioning

confidence: 96%

Thyroid hormones control lysosomal enzyme activities in liver and skeletal muscle

DeMartino

Goldberg

1978

Proc. Natl. Acad. Sci. U.S.A.

133

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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...

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“…Although the exact reason for the disparity is not clear at present, the difference in the experimental settings may be one of the major sources of the disparity. It should be noted that the respiratory activity differs depending on the age of animals [19], the constituents of incubation medium, respiratory substrates, and the presence or absence of ADP and the ATP-trapping system (hexokinase plus glucose). Similarly, the phosphorylation efficiency has been reported either increased [I21 or decreased [9, 141. In the present study, liver mitochondria from hypothyroid rats were shown to exhibit a normal activity in succinate dehydrogenase and a near normal activity in the succinoxidase system.…”

Section: Resultsmentioning

confidence: 99%

Alterations of oxidative phosphorylation reactions in mitochondria isolated from hypothyroid rat liver

Ezawa

Yamamoto

Kimura³

et al. 1984

European Journal of Biochemistry

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1. Several parameters of oxidative phosphorylation reaction were studied in vitro in isolated liver mitochondria from hypothyroid rats.2. When succinate was employed as a respiratory substrate for mitochondria incubated in a mannitol/sucrose/ phosphate buffer, and measurements were performed during initial additions of ADP, the magnitude of state 3 and state 4 respiration was not different between mitochondria from the hypothyroid and those from the control rats.3. During the course of repetitive additions of ADP and consequently of sequential transitions from state 4 to state 3 and back to state 4, mitochondria from hypothyroid animals showed a gradual decline in the rate of both state 3 and state 4 respiration whereas those from normal animals did not. The total succinate dehydrogenase activity was not different between the two types of mitochondria, and the decline in state 3 and state 4 respiration was not accompanied by any change in the apparent K, for ADP or in the corrected ADPjO ratio [Biochem. Biophys. Res. Commun. (1973) 53, 9881. 4. The amount of oxygen consumed during the state-4-3+4 transition was lower in the hypothyroid than in the control mitochondria.5. These alterations were reversed if the hypothyroid animals were injected with thyroxine intraperitoneally (2 pg/l00 g body weight) for 3 weeks before isolation of mitochondria.6. These results indicate that the fall of respiratory activity in hypothyroidism may result from the decrease not only of respiratory activities of state 3 and state 4, but also of the energy spent in the process of the state-4+3+4 transition, while the coupling efficiencyper se remains normal. These properties become manifest when mitochondria respond to pulses of ADP load, a situation likely to occur in situ.Alteration in the tissue respiratory activity is one of the most characteristic metabolic changes observed in thyroid dysfunction. Various attempts have been made to attribute this change in respiratory activity to an influence of thyroid hormone directly upon the process of oxidative phoshorylation. Earlier reports demonstrated that thyroxine in vitro caused an uncoupling of oxidative phosphorylation [l], and the same hormone in vivo an increase in the transmembrane protonic electrochemical potential difference and the respiratory rate [2].However, in these experiments unphysiologically high doses of thyroxine (up to 1 mM thyroxine in experiments in vitro, and 800 mg of thyroxine subcutaneouslyJkg body weight in vivo experiments) were used [l, 21, and later work has not confirmed this concept. Because thyroid hormone is needed for normal development and maintenance of normal functions of many organs, another naive scepticism concerns with the biological significance of uncoupling of oxidative phosphorylation and of an increase in the transmembrane potential difference.Enq~mex Succinate dehydrogenase or succinate: 2,6-dichloroindophenol oxidoreductase (EC 1.3.99.1); phospholipase A from Crotalus terrificus (EC3.1.1.4).As an attempt to elucidate the mechanism of r...

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Role of the pituitary and thyroid glands in the decline of minimal O2 consumption with age.

Cited by 105 publications

References 25 publications

Interaction of Age and Thyroid Hormone Status on Beta-Endorphin Content in Rat Corpus Striatum and Hypothalamus

Interaction of Age and Thyroid Hormone Status on Beta-Endorphin Content in Rat Corpus Striatum and Hypothalamus

Thyroid hormones control lysosomal enzyme activities in liver and skeletal muscle

Alterations of oxidative phosphorylation reactions in mitochondria isolated from hypothyroid rat liver

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