The effect of tri-iodothyronine administration on protein synthesis in the diabetic rat.
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ABSTRACT:
SUBMITTER: Brown JG
PROVIDER: S-EPMC1152291 | biostudies-other | 1983 Aug
REPOSITORIES: biostudies-other
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Project description:The dynamics of the induction of nuclear tri-iodothyronine receptors and mitochondrial alpha-glycerophosphate dehydrogenase were studied in rat liver after a single injection of tri-iodothyronine. The maximal binding capacity (C(max.)) and association constant (K(a)) of the nuclear receptors were determined by Scatchard analyses with and without correction for the endogenous tri-iodothyronine measured by radioimmunoassay. The administration of tri-iodothyronine induced sequential increases in the concentration of nuclear receptors and alpha-glycerophosphate dehydrogenase activity in the liver. The nuclear-receptor concentration was increased to 2.5 times that in the hypothyroid rat 1 day after the administration of hormone, and then decreased, with a half-life of about 2 days. alpha-Glycerophosphate dehydrogenase activity changed in parallel with the nuclear-receptor concentration, showing a delayed response. The total amount of non-histone protein in the liver was significantly increased 3 days after the administration. It seems likely therefore that the tri-iodothyronine-induced increase in nuclear-receptor concentration is responsible, at least in part, for the induction of this enzyme. The possibility is also suggested that nuclear receptors may be one of the non-histone proteins selectively synthesized at an early stage of the hormonal stimulation. Throughout the time course, the K(a) values of the nuclear receptors for tri-iodothyronine remained unchanged, when corrected for endogenous tri-iodothyronine bound to the non-histone proteins, although they were apparently changed when the correction was not made. The results obtained provide further evidence for hormonal modulation of the nuclear receptors which is closely linked with the hormonal effect.
| S-EPMC1161318 | biostudies-other
Project description:In an effort to determine the physiological significance of previous studies showing stimulation of microsomal protein synthesis by thyroxine added in vitro, an early effect of tri-iodothyronine injected in vivo was sought. Tri-iodothyronine (25 micrograms/100 g) administered to euthyroid rats stimulated microsomal protein synthesis in vitro within 3--6 h. This effect occurred much earlier than the 26 h lag previously reported after tri-iodothyronine administration to hypothyroid rats. This early effect of tri-iodothyronine on protein synthesis is prevented by alpha-amanitin, suggesting that it is dependent on RNA synthesis. The failure to find a direct effect in vivo of tri-iodothyronine on translation casts doubt on the physiological significance of previous studies that have shown a direct stimulation of translation by thyroxine added in vitro.
| S-EPMC1161397 | biostudies-other
Project description:1. Rat liver mitochondria were separated into heavy, light and fluffy fractions by differential centrifugation under standard conditions. 2. All mitochondrial fractions possessed soluble as well as membrane-bound enzymes typical of mitochondria. 3. The heavy fraction represented the stable mitochondrial structures and the fluffy particles appear to be loosely coupled. 4. The light mitochondrial fraction lacked the ability of coupled phosphorylation. 5. A study of mobility and isoelectric pH indicated a similarity in the basic membrane structure of all the mitochondrial fractions. 6. The turnover rates of proteins in the heavy and fluffy particles were almost identical; however, this rate was rapid for the light mitochondrial fraction. 7. On treatment with 3,3',5-tri-iodo-l-thyronine, succinoxidase activity was maximally stimulated much earlier in the light mitochondrial fraction than in the heavy fraction. The activity of the fluffy particles, however, remained almost unaffected. 8. Malate dehydrogenase activity in all the mitochondrial fractions was stimulated only at 40h after tri-iodothyronine treatment. 9. The pattern of incorporation of dl-[1-(14)C]leucine in vivo in the tri-iodothyronine-treated animals indicated a rapid initial incorporation and high synthetic ability of the light mitochondrial fraction. 10. The turnover pattern of proteins of the mitochondrial fractions from animals receiving repeated doses of tri-iodothyronine was remarkably different from the normal pattern and suggested that preformed soluble protein units may be incorporated in the light mitochondrial fraction during maturation to form the stable heavy mitochondria. 11. The amount of light-mitochondrial proteins decreased by 40% on thyroidectomy and increased by 160% on treatment with tri-iodothyronine. 12. The possible significance of these results is discussed in relation to mitochondrial genesis.
| S-EPMC1179087 | biostudies-other
Project description:The effect of long-term administration of small amounts of tri-iodothyronine was examined on the nuclear tri-iodothyronine receptors in rat liver. The maximal binding capacity (C(max.)) and association constant (K(a)) of the receptors were determined in thyroidectomized rats given vehicle alone (group A), 2mug of tri-iodothyronine/100g body wt. (group B) or 7mug of tri-iodothyronine/100g body wt. (group C) for 2 weeks. Scatchard analyses with correction for the amount of endogenous tri-iodothyronine revealed that C(max.) values per g of liver were increased to 1.5 and 2.7 times the control value in groups B and C respectively. Since concentrations of DNA per g of liver were significantly increased in the two groups of hormone-treated rats, C(max.) values per mg of DNA were nearly the same in group B, but still increased significantly in group C compared with group A. K(a) values remained unchanged in all three groups of animals. Mitochondrial alpha-glycerophosphate dehydrogenase activity was 9.6 and 28.7 times as high in groups B and C, respectively, as in group A. Concentrations of endogenous tri-iodothyronine bound to non-histone protein were substantially increased in groups B and C, although concentrations of serum tri-iodothyronine remained rather low. The results obtained indicate that the long-term administration of tri-iodothyronine in small doses induces an increase in the nuclear receptors associated with increased DNA with and without accompanying a relative increase in the receptor concentration in thyroidectomized rats. Also the hormonal effect is closely related to the total number of the nuclear receptors and the concentrations of nuclear tri-iodothyronine bound to the receptors rather than the serum tri-iodothyronine concentrations.
| S-EPMC1161684 | biostudies-other
Project description:Salmon calcitonin has chondroprotective effect both in vitro and in vivo, and is therefore being tested as a candidate drug for cartilage degenerative diseases. Recent studies have indicated that different chondrocyte phenotypes may express the calcitonin receptor (CTR) differentially. We tested for the presence of the CTR in chondrocytes from tri-iodothyronin (T3)-induced bovine articular cartilage explants. Moreover, investigated the effects of human and salmon calcitonin on the explants.Early chondrocyte hypertrophy was induced in bovine articular cartilage explants by stimulation over four days with 20 ng/mL T3. The degree of hypertrophy was investigated by molecular markers of hypertrophy (ALP, IHH, COLX and MMP13), by biochemical markers of cartilage turnover (C2M, P2NP and AGNxII) and histology. The expression of the CTR was detected by qPCR and immunohistochemistry. T3-induced explants were treated with salmon or human calcitonin. Calcitonin down-stream signaling was measured by levels of cAMP, and by the molecular markers.Compared with untreated control explants, T3 induction increased expression of the hypertrophic markers (p<0.05), of cartilage turnover (p<0.05), and of CTR (p<0.01). Salmon, but not human, calcitonin induced cAMP release (p<0.001). Salmon calcitonin also inhibited expression of markers of hypertrophy and cartilage turnover (p<0.05).T3 induced early hypertrophy of chondrocytes, which showed an elevated expression of the CTR and was thus a target for salmon calcitonin. Molecular marker levels indicated salmon, but not human, calcitonin protected the cartilage from hypertrophy. These results confirm that salmon calcitonin is able to modulate the CTR and thus have chondroprotective effects.
| S-EPMC3386925 | biostudies-literature
Project description:Leptin, the product of the obese gene, is produced by white adipocytes. The release of leptin, as well as leptin mRNA content, was enhanced in adipocytes isolated from hypothyroid rats. The administration of tri-iodothyronine (T3) 8 h before death inhibited leptin release by adipocytes incubated for 6 or 24 h. Direct addition of T3 to pieces of adipose tissue enhanced the loss of leptin mRNA seen over 24 h in the presence of dexamethasone plus the beta3-adrenergic agonist Cl 316,243. In contrast, if pieces of adipose tissue were incubated with dexamethasone plus insulin, enhanced the T3 accumulation of leptin mRNA. These results indicate that T3 enhances net adipocyte leptin mRNA accumulation in a condition that approximates the fed state (presence of insulin) but inhibits leptin mRNA accumulation in a condition that approximates the fasted state (absence of insulin).
| S-EPMC1219490 | biostudies-other
Project description:The short-term effect of L-tri-iodothyronine (T3) on hepatic Ca2+ uptake from perfusate was compared with changes induced by T3 on cellular respiration and glucose output in isolated perfused livers from fasted and fed rats. The same parameters were also studied after the addition of glucagon or vasopressin. T3 (1 microM) induced Ca2+ uptake from the perfusate into the liver within minutes, and the time course was similar to that for stimulation of respiration and gluconeogenesis in livers from fasted rats, and for the stimulation of respiration and glucose output in livers from fed rats. The effects were dose-dependent in the range 1 microM-0.1 nM. Similar changes in the same parameters could be observed with glucagon and vasopressin, but with a completely different time course. Also, the influence of the T3 analogues L-thyroxine (L-T4), 3,5-di-iodo-L-thyronine (L-T2) and 3,3',5-tri-iodo-D-thyronine (D-T3) on hepatic energy metabolism was examined. Whereas D-T3 had practically no effect, L-T4 and L-T2 caused changes in Ca2+ uptake, O2 consumption and gluconeogenesis in livers from fasted rats similar to those with T3. It is concluded that changes in mitochondrial and cytosolic Ca2+ concentrations are involved in the stimulation of respiration and glucose metabolism observed with T3, glucagon and vasopressin.
| S-EPMC1138370 | biostudies-other
Project description:Isolated rat renal tubules prepared by collagenase digestion were used to study the effects of 3,3',5'-tri-iodothyronine ('reverse T3', rT3) and other iodothyronines on the formation of 3,3',5-tri-iodothyronine (T3) from thyroxine (T4). rT3 inhibited the conversion with a dose response over the concentration range 1.5nM-1.5microM. The inhibition was competitive in nature. Both 3,3'-di-iodothyronine and 3',5'-di-iodothyronine also inhibited the production of T3 and T4 in isolated rat renal tubules, but tetraiodothyroacetic acid and 3,5-di-iodothyronine were found to have no effect. These experiments demonstrate in an intact cell system that some naturally occurring iodothyronines have significant effects on T4 deiodination.
| S-EPMC1162087 | biostudies-other
Project description:Gestational Diabetes Mellitus (GDM) is characterized by abnormal maternal D-glucose metabolism and altered insulin signaling. Dysregulation of thyroid hormones (TH) tri-iodethyronine (T3) and L-thyroxine (T4) Hormones had been associated with GDM, but the physiopathological meaning of these alterations is still unclear. Maternal TH cross the placenta through TH Transporters and their Deiodinases metabolize them to regulate fetal TH levels. Currently, the metabolism of TH in placentas with GDM is unknown, and there are no other studies that evaluate the fetal TH from pregnancies with GDM. Therefore, we evaluated the levels of maternal TH during pregnancy, and fetal TH at delivery, and the expression and activity of placental deiodinases from GDM pregnancies. Pregnant women were followed through pregnancy until delivery. We collected blood samples during 10-14, 24-28, and 36-40 weeks of gestation for measure Thyroid-stimulating hormone (TSH), Free T4 (FT4), Total T4 (TT4), and Total T3 (TT3) concentrations from Normal Glucose Tolerance (NGT) and GDM mothers. Moreover, we measure fetal TSH, FT4, TT4, and TT3 in total blood cord at the delivery. Also, we measured the placental expression of Deiodinases by RT-PCR, western-blotting, and immunohistochemistry. The activity of Deiodinases was estimated quantified rT3 and T3 using T4 as a substrate. Mothers with GDM showed higher levels of TT3 during all pregnancy, and an increased in TSH during second and third trimester, while lower concentrations of neonatal TT4, FT4, and TT3; and an increased TSH level in umbilical cord blood from GDM. Placentae from GDM mothers have a higher expression and activity of Deiodinase 3, but lower Deiodinase 2, than NGT mothers. In conclusion, GDM favors high levels of TT3 during all gestation in the mother, low levels in TT4, FT4 and TT3 at the delivery in neonates, and increases deiodinase 3, but reduce deiodinase 2 expression and activity in the placenta.
| S-EPMC7685482 | biostudies-literature
Project description:Glucokinase (EC 2.7.1.2) first appears in the liver of the rat 2 weeks after birth and increases after weaning on to a high-carbohydrate diet. We investigated the hormonal regulation of glucokinase (GK) mRNA in primary cultures of hepatocytes from 10-12-day-old suckling rats. GK mRNA was undetectable in such cells after 48 h of culture in serum-free medium devoid of hormones. Addition of insulin or tri-iodothyronine (T3) to the medium resulted in induction of GK mRNA. The effects of insulin and T3 were dose-dependent and additive. Dexamethasone alone did not induce GK mRNA, but enhanced the response to insulin and decreased the response to T3. Induction of GK mRNA by insulin was not affected when the medium glucose concentration was varied between 5 and 15 mM, nor when culture was conducted in glucose-free medium supplemented with lactate and pyruvate or galactose. The time course of initial accumulation of GK mRNA in response to insulin was characterized by a lag of 12 h and an induction plateau reached after 36 h. If hepatocytes were then withdrawn from insulin for 24 h and subsequently subjected to a secondary stimulation by insulin, GK mRNA re-accumulated with much faster kinetics and reached the fully induced level within 8 h. Both primary and secondary responses to insulin were abolished by actinomycin D. These results provide insight into the role of hormonal stimuli in the ontogenic development of hepatic glucokinase.
| S-EPMC1149602 | biostudies-other