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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the effect of starvation, oral and i.v. nutriments, and hypothyroidism on the peripheral conversion of thyroxine (T4) to 3,3', 5-triiodothyronine (T3) in the rat and mouse, an in vitro system for assessing T4 conversion to T3 by fresh liver homogenates was used. A 2-day starvation in the rat reduced hepatic T3 generation from T4 by 47% +/- 3.5% (mean +/- SE) in six separate experiments and also impaired the metabolism of 125I-r-T3. Administration of carbohydrate (CHO) and amino acids (P), but not lipid (L), significantly increased T3 generation above values observed in the starved rat. The mean serum glucose concentration was similar in all nutriment-infused groups, but serum insulin was significantly greater in the CHO- and P-infused as compared to the L-infused rats. These findings suggest that CHO and P, but not L, are important modulators of hepatic outer ring thyronine deiodination in the rat, perhaps due to increased intracellular glucose. Hypothyroidism in the rat induced by thyroidectomy and congenital secondary hypothyroidism in the dwarf mouse resulted in a striking decrease in hepatic conversion of T4 to T3. This decrease was restored to normal by the daily s.c. administration of physiologic doses of T4 (1.5 microgram/100 g) or T3 (0.5 microgram/100 g) for 14 days, and was increased above normal following treatment of normal rate with greater than physiologic doses of T4 (3microgram/100 g) or T3 (1 microgram/100g). In vitro hepatic conversion of T4 to T3 is, therefore, dependent upon thyroid function. Since 2-days starvation in the rat was associated with decreased serum concentrations of T4, T3, and TSH, and hypothyroidism resulted in decreased conversion of T4 to T3, the effect of a constant 2-day infusion of physiologic doses of T4 or T3 in the starved rat on the in vitro deiodination of T4 was assessed. Thyroid hormone replacement did not enhance the conversion of T4 to T3 in the starved rat. These observations suggest that the starvation-induced decrease in hepatic generation of T3 from T4 is not due to hypothyroidism and that the mechanism(s) of the decreased T3 production observed in starvation and hypothyroidism is different.
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PMID:Effect of starvation, nutriment replacement, and hypothyroidism on in vitro hepatic T4 to T3 conversion in the rat. 3 20

Thyroid hormones act at the transcriptional level in the induction of the important hepatic glucoregulatory enzyme PEP-carboxykinase and glucokinase (Fig. 1 and Fig. 2). They have no significant effect on the degradation of both enzymes, nor on the degradation of the specific mRNAs. A T3-receptor interaction is essential for their effect. Suggestions have been made for a thyroid hormone regulatory element in the promotor region of T3-dependent genes (for a review see [18]). Thyroid hormones probably do not determine the direction of the metabolic flux; however, they significantly enhance in a permissive way the transition from one state, e.g. starvation, to another, e.g. refeeding. And by enhancing significantly the activity of important regulatory enzymes, they enhance the flux of metabolites under different metabolic conditions, such as in starvation or after refeeding.
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PMID:Role of thyroid hormones in the regulation of hepatic glucokinase and phosphoenolpyruvate-carboxykinase gene expression during the starvation-refeeding transition. 208 92

Thyroid hormone nuclear receptor molecules have been characterized as proteins of approximately 49,000 molecular weight existing in cells attached to chromatin and with 4000-8000 copies per nucleus. They bind T3 with Ka of 0.2 X 10(10) l/mol and show microheterogeneity on isoelectric focusing. Hormone responsiveness varies with receptor content in the nucleus and occupancy of receptor by T3. Recent investigations have shown that the receptors are part of the v-erbA related super family of nuclear hormone receptors. At least two types of T3 receptors (TR) exist, one coded by a gene on chromosome 3 (TR beta) and a second coded on chromosome 17 (hTR alpha). Receptors are low in the fetus and, in the adult, are dramatically reduced by starvation, illness and glucagon. Receptors function through binding of T3 or other hormone analogs to a domain in the carboxyl portion of the protein, and binding of the receptor-T3 complex through 'DNA-fingers' to specific response elements as enhancers and located in the 5'-flanking DNA of thyroid hormone responsive genes. Extensive studies on regulation of rat growth hormone have suggested binding of receptor or associated factors to several positions in the 5'-flanking DNA, and recent studies suggest that a crucial area may be a 15 bp segment between bases -179 and -164. Abnormal receptors are believed to be responsible for the syndrome of generalized resistance to thyroid hormone action, but it is yet unclear as to which form (or forms) of the receptor is abnormal in this syndrome.
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PMID:Thyroid hormone nuclear receptors and their role in the metabolic action of the hormone. 249 27

Thyroid hormones contribute to the regulation of blood sugar by accelerating the turnover of glucose. The mechanism by which thyroid hormones stimulate the rate of glucose utilization in the liver was determined by investigating the effect of different thyroid states on the expression of the glucokinase gene, a key enzyme of glycolysis. In euthyroid rats the mass of glucokinase mRNA increased 8-fold during the first 4 h of refeeding a high carbohydrate diet to 48-h starved rats. In hypothyroid rats under the same conditions only a 2-fold induction was observed. In euthyroid rats a 5-fold increase was obtained 1 h after refeeding, while hypothyroid rats displayed no significant response in glucokinase mRNA within this time. Basal levels of glucokinase mRNA in starved rats were the same observed in eu- and hypothyroid rats. Injection of 3,3',5-triiodothyronine (T3) into hypothyroid rats restored the mRNA levels of refed hypothyroid rats to euthyroid levels within 24 h. However, a 3-fold increase over untreated animals was already observed 3 h after T3 administration. Even subphysiological doses of T3 (0.1 microgram/100 g body weight) led to an significant increase in glucokinase mRNA levels (1.5-fold, p less than 0.05) in hypothyroid rats, whereas higher doses (100 micrograms/100 g body weight) restored the mRNA levels to those of euthyroid controls. Parallel increases in the cytosolic mRNA levels and rate of glucokinase gene transcription were detected when hypo- and euthyroid fasted rats were compared after 4 h of refeeding. It is concluded that thyroid hormones are permissive for the induction of glucokinase during refeeding but have no effect during starvation. They rapidly enhance the rate of gene transcription within the range of their physiologically circulating concentrations. The results suggest a major importance of thyroid hormones in regulating glucose utilization.
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PMID:Effect of thyroid hormones on glucokinase gene transcription in rat liver. 258 35

Thyroid function was investigated in rats treated sc with a single injection of human recombinant interleukin-1 beta (hrIL-1). In 5 h 12.5 micrograms hrIL-1 decreased total serum T4 levels by 30 +/- 2% (P less than 0.01) and serum T3 levels by 35 +/- 4% (P less than 0.001). However free T4 and T3 fractions increased markedly within the first 140 min by 162 +/- 20% (P less than 0.001) and by 55 +/- 4% (P less than 0.001) resulting in a 88 +/- 20% increase in the free T4 concentration (P less than 0.001) but no increase in the free T3 concentration. Serum TSH concentration fell in the 5 h after the hrIL-1 injection by 77 +/- 3% (P less than 0.001). A similar decrease was observed with 0.125 micrograms hrIL-1. Five hours of starvation did not change serum TSH levels, suggesting that the effect of hrIL-1 on TSH was not due to decreased food intake. In order to test whether the decrease in serum TSH was due to an intrapituitary increase in T3, hrIL-1 was injected in hypothyroid rats: the fall of serum TSH was not prevented and it fell in 5 h from 14.05 +/- 0.56 to 9.66 +/- 0.98 ng/ml (31%, P less than 0.01, n = 14). These results suggest that hrIL-1 acts independently of thyroid hormones. Peripheral metabolism of T4 was studied by implanting [125I]T4 secreting minipumps during 14 days. There was no difference in T4 plasma clearance rate between control and treated animals. The fall of serum T4 was therefore explained by decreased secretion and not by increased catabolism since ether link cleavage of T4 and changes in hepatic deiodinase could not be detected. We therefore suggest that hrIL-1 inhibits thyroid function mainly at the hypothalamic-hypophyseal level.
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PMID:Human recombinant interleukin-1 beta decreases plasma thyroid hormone and thyroid stimulating hormone levels in rats. 326 3

Abnormal thyroid function in patients with eating disorders can result from malnutrition. A low serum triiodothyronine (T3) level is commonly noted in starvation states and is caused by reduced peripheral conversion of thyroxine (T4) to T3. Diminished T4 concentrations are also observed. Adequate nutrition normalizes this type of aberrant laboratory profile. Thyroid function tests that give results below the normal range are best repeated initially for verification of results and again after adequate nutrition is reestablished. If no primary endocrinopathy is present, spontaneous correction of these laboratory values can be expected with conventional dietary habits.
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PMID:How do eating disorders affect thyroid function? 347 68

Thyroid-stimulating hormone (TSH) alpha- and beta-subunit glycosylation was investigated in mouse thyrotropic tumor and in normal and hypothyroid pituitary cells for various periods of time in the presence of [3H]mannose or [3H]galactose. After sequential precipitation with anti-alpha and anti-beta sera, subunits were treated with Pronase followed by endo-beta-N-acetylglucosaminidase H (Endo H) and analyzed by paper chromatography. In primary cultures of thyrotropic tumor cells incubated for 60 min with [3H]mannose, primarily Man9GlcNAc and Man8GlcNAc were found on TSH + alpha subunits, whereas Glc1Man9GlcNAc and Man9GlcNAc were prominent on free beta subunits. After preincubation of cells for 16 h in the presence or absence of glucose followed by a 60-min pulse of [3H]mannose, there was an 8-fold increase in labeled TSH + alpha but only a minimal change in free beta or total proteins. In the absence of glucose, there was a selective accumulation of Man8GlcNAc on TSH + alpha but not on free beta or total proteins; however, there was no detectable accumulation of Endo H resistant forms during glucose starvation on TSH subunits or total proteins. Normal mouse and rat pituitary minces incubated for 60 min with either [3H]mannose or [3H]galactose showed no glucose-containing species on TSH subunits, but equal amounts of Man9GlcNAc and Man8GlcNAc on TSH + alpha, and mostly Man9GlcNAc on free beta subunits. In contrast, hypothyroid mouse and rat pituitaries exhibited an increase in Glc1Man9NAc and Glc1Man8GlcNAc on free beta but not on TSH + alpha or total proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential processing and regulation of thyroid-stimulating hormone subunit carbohydrate chains in thyrotropic tumors and in normal and hypothyroid pituitaries. 407 17

Thyroid hormone metabolism and plasma concentrations of TSH were studied after short-term hypocaloric refeeding of rats starved for 2-6 days. Carbohydrate and protein (10 kcal) refeeding after 4 days of starvation resulted in a rapid increase in serum T3 (P less than 0.01) and, less consistently of T4. Plasma TSH did not change. These findings were not due to changes in the metabolic clearance rates or in thyroid hormone binding proteins, as the disappearance of injected labelled T3 and T4, and the free fractions of T3 and T4, were unchanged. Increased thyroidal secretion, and for T3, increased peripheral conversion from T4 were therefore responsible for these changes. Fat refeeding had no immediate effect on plasma T4, T3 or TSH. After 6 days of starvation, refeeding of any nutrient was ineffective in altering the plasma concentrations of T3 and T4. The intraperitoneal administration of nicotinamide (100 mg/100 g body weight) to starving animals caused an increase in blood glucose and a decrease in blood beta-hydroxybutyrate similar to that which followed carbohydrate refeeding; T3, however, did not increase. In spite of producing a profile of substrates in the serum similar to that found following carbohydrate refeeding, nicotinamide administration had no effect on the blood lactate/pyruvate ratio which was increased following carbohydrate refeeding. Therefore, the cytoplasmic redox state, as reflected by the lactate/pyruvate ratio, may be closely related to the control of peripheral thyroid hormone metabolism.
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PMID:Interrelationships between energy metabolism and thyroid hormone metabolism during starvation in the rat. 644 70

Thyroid hormone effects have been studied in both rats and human. In rats ketone body levels are increased by thyroid hormone excess at the initial phase of starvation. Glucose levels are also increased at the initial and late phase of starvation. Ketone bodies production of isolated liver cells from thyroidectomized fed rats (14 +/- 0,2 muMol/g/h) are decreased when compared with cells from thyroidectomized fed rats treated with triiodothyronine 63 +/- 3 muMol/g/h). These changes are related to a direct effect of T3. Ketone bodies levels are increased in Grave's diseases. The increase is significantly correlated to thyroid hormone levels.
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PMID:[Effect of thyroid function on ketogenesis (author's transl)]. 724 39

The Akt/protein kinase B serine/threonine kinase is a downstream effector of phosphoinositide 3-kinase (PI3K). Akt is an important component of mitogenic and antiapoptotic signaling pathways and is implicated in neoplastic transformation. Thyroid cells in culture retain a differentiated phenotype consisting of epithelial cell morphology and the expression of several tissue-specific genes. The survival and proliferation of these cells depend on thyrotropin and a mixture of five additional hormones that includes insulin. The regulation of proliferation and the expression of the thyroid differentiation program are intimately connected processes. As a result, oncogenes that induce hormone-independent proliferation invariably impair the expression of the thyroid-specific differentiation markers. Given that thyrotropin and insulin stimulate Akt activation in thyroid cells, we set out to determine the effects of Akt on thyroid cell proliferation, survival, and differentiation. To this end, we expressed constitutively active myristylated Akt (myrAkt) in PC Cl 3 thyroid cells. The myrAkt-expressing cells continued to proliferate, even in the absence of hormones, and they were resistant to programmed cell death induced by starvation. These effects were paralleled by the induction of the G1 cyclins D3 and E and by the inhibition of induction of the proapoptotic Fas, Fas ligand, and BAD genes in starved cells. However, in marked contrast with several other oncogenes, myrAkt did not interfere with the expression of thyroid differentiation functions. These results unveil the existence of an Akt-triggered thyroid cell pathway that modulates proliferation and survival without affecting the expression of the thyroid cell differentiated phenotype.
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PMID:Akt/protein kinase B promotes survival and hormone-independent proliferation of thyroid cells in the absence of dedifferentiating and transforming effects. 1091 69


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