Liver thyroid hormones effect

Thyroid hormone effects on metabolism arc diverse. The rates of protein and carbohydrate synthesis and catabolism are inlluenced. An example of the effect of thyroid hormones on lipid metabolism is the observation of a high serum cholesterol in some hypothyroid patients. This is a consequence of a reduction in cholesterol metabolism due to down regulation of low-density lipoprotein (LDL) receptors on liver cell membranes, with a subsequent failure of sterol excretion via the gut. 

Apletalina, E.V, H.C. Li, and D.J. Waxman (2003). Evaluation of thyroid hormone effects on liver P450 reductase translation. Arch. Biochem. Biophys. 409, 172-179. 

Z)-2,3-Methanothyronine 59 and its dibromo derivative 60 have comparable activity with the thyroxine 61, a thyroid hormone [66], which exhibited thyro-mimetic activities in basal metabolism and antigoiter tests (comparison of oxygen consumption and heart rate in normal and thyroidectomized rats) but did not have an inhibitory action on the metabolism developed by triiodothyronine [66]. (Z)-2,3-Methanohistidine 62, tested on rat liver, is an effective inhibitor of histidine decarboxylase, Eq. (23) [67]. 

Mechanism of Action A thioimidazole derivative that inhibits synthesis of thyroid hormone by interfering with the incorporation of iodine into tyrosyl residues. Thera-peuticEffect Effectively treats hyperthyroidism by decreasingthyroid hormone levels. Pharmacohinetics Rapid absorption following PO administration. Protein binding Not significant. Widely distributed throughout the body. Metabolized in liver. Excreted in urine. Half-life 5-6 hr. 

Thyroid hormones exert their effect by binding to nuclear receptors in target organs. Both the thyroid hormones are well absorbed after oral administration. They are conjugated with sulfuric acid in liver and excreted in bile. 

Thyroid effects were produced in rats in acute-duration studies at doses as low as 3 mg/kg/day (reduced serum levels of T4 hormone) but not at 1 mg/kg/day, in intermediate-duration studies at doses as low as 0.05 mg/kg/day (increased number and decreased size of follicles), and in chronic-duration studies at doses as low as 1.3 mg/kg/day. The no-observed-adverse-effect level (NOAEL) of 1 mg/kg/day is used herein as the basis for an acute-duration minimal risk level (MRL) for oral exposure. The acute-duration lowest-observed-adverse-effect level (LOAEL) for hepatic effects is identical to the LOAEL for acute thyroid toxicity, but is a less appropriate basis for the MRL because organ functional implications are not as clear. The intermediate-duration LOAELs for thyroid and hepatic effects are also comparable to each other, but neither of these LOAELs are suitable for an intermediate MRL because reproductive and developmental toxicity occurred at a lower dosage. The thyroid LOAEL for chronic-duration exposure is unsuitable for deriving a chronic MRL because decreased survival occurred at the same dose (lower doses were not tested), and thyroid, liver, and other effects occurred at lower doses in intermediate-duration studies. 

Available intermediate- and chronic-duration oral studies in animals indicate that the thyroid and liver are the main systemic targets of PBDE toxicity as shown by effects mainly including enlargement and histological alterations in both organs and changes in serum levels of thyroid hormones. Several acute-duration studies of pentaBDE suggest that immunosuppression may also be an important health end point. Very little information is available on potential neurotoxic effects of PBDEs, mainly the results of three... 

People with exposure to anti-thyroid drugs (e.g., lithium), thyroid disease, or otherwise compromised thyroid function might have a more pronounced response to PBBs and PBDEs because of their underlying limitations in thyroid hormone production. Similarly, people with compromised function of other organs, such as those with liver or kidney diseases (e g., liver cirrhosis or hepatitis B), could be considered more susceptible to health effects of PBBs and PBDEs. 

Thyroid hormones are intimately involved in regulating the basal metabolic rate. Liver tissue of animals given excess thyroxine shows an increased rate of 02 consumption and increased heat output (thermogenesis), but the ATP concentration in the tissue is normal. Different explanations have been offered for the thermogenic effect of thyroxine. One is that excess thryroxine causes uncoupling of oxidative phosphorylation in mitochondria. How could such an effect account for the observations Another explanation suggests that the thermogenesis is due to an increased rate of ATP utilization by the thyroxine-stimulated tissue. Is this a reasonable explanation Why ... 

Uzzan B, Nicolas P, Perret G, Vassy R, Tod M, Petitjean O. Effects of troleandomycin and josamycin on thyroid hormone and steroid serum levels, liver function tests and microsomal monooxygenases in healthy volunteers a double blind placebo-controlled study. Fundam Clin Pharmacol 1991 5(6) 513-26. 

Guggulsterones Z and E seem to have the greatest effect upon stimulation of thyroid hormone, though other substrates of the herb commiphora mukul may effect different metabolic factors as well. Thus far, research suggests this is a result of guggulsterones Z E stimulation of TSH (Thyroid-Stimulating-Hormone) production. This results in an increase in Thyroid gland T-4 production and subsequent liver conversion to the more active T-3 hormone. 

Visser TJ, Kaptein E, van Toor H, et al. Glucuronidation of thyroid hormone in rat liver effects of in vivo treatment with microsomal enzyme inducers and in vitro assay conditions. Endocrinology 1993 133 2177-2186. 

Membrane-containing fractions displaying T3-binding activities have been detected in a variety of cell types [13-16], Rat liver [15] and erythrocyte [16] plasma membranes, for instance, contain T4- and T3-binding sites with affinities ranging from 1 to 10 x 10 10 M for T3. It is not clear whether the function of these sites is related to the transport of thyroid hormones from the blood to the cell or if they represent receptors responsible for non-nuclear effects of thyroid hormones [17,18]. 

Another major lipogenic enzyme, fatty acid synthase, is also regulated in the liver by nutritional status, insulin, glucagon and T3. Wilson et al. [78] have found that stimulation of fatty acid synthase requires both thyroid hormones and insulin (40-fold stimulation), whereas T3 or insulin alone had much smaller effects (2.5.-fold). Experiments performed in the presence or the absence of puromycin suggest that a common T3-induced peptide intermediate regulates the level of both fatty acid synthase and malic enzyme mRNAs. 

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