[LATS-the extrapituitary thyroid stimulator and its role in the etiology and pathogenesis of Graves-Basedow disease].
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Biomedical subjects
Publications and source records attributed to J Nauman.
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Specific activity of T4-5'-deiodinase, the enzyme which catalyze peripheral production of triiodothyronine (T3) from thyroxine (T4) has been evaluated in the subcutaneous adipose tissue of obese patients. In lean healthy women (BMI less than 21) mean activity of T4-5'-D was found to be 122 +/- 29.4 fmol T3/mg of protein/min and was higher then respective activity of the enzyme in adipocytes of patients with mild obesity (22 less than BMI less than 30) where the mean was 92.14 +/- 18.05 fmol T3/mg/min. The activity of T4-5'-D was significantly decreased in patients with severe obesity (BMI less than 30) when compared with respective activity of the enzyme found in controls (47.36 +/- 18.4 fmol T3/mg/min vs 122.4 +/- 29.4 fmol T3/mg/min; p less than 0.01). As T4-5'-D in human adipose tissue has been previously characterized as type II of the enzyme, diminished activity found in obese subjects means that thyroid metabolic activity of adipocyte is decreased. Such a state would lead to antilipolytic action of catecholamines in obesity.
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Effects of thyroxine (T4), triiodothyronine (T3) or reverse-triiodothyronine (rT3) in vivo pretreatment or the effect of hypothyroidism on properties of beta-adrenoreceptors in the rat heart were investigated. beta-adrenergic antagonist hydroxybenzylpindolol (HYP125I) was used to estimate the maximal binding capacity (MBC) and the affinity (KD) of beta-adrenoreceptors. Both T4 and T3 in dose and time dependent manner increased MBC value but only slightly and insignificantly affected affinity of the beta-adrenoreceptor. The effect of T3 on MBC was higher than that of an equal dose of T4, but the latter effect persisted longer than that of T3. Hypothyroidism decreased MBC value, but increased the affinity of beta-adrenoreceptors. Pretreatment of rats with rT3 produced changes in beta-adrenoreceptors similar to those seen in hypothyroid rats.
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The properties of the thyroid hormone binding to rat heart cytosol were studied. Cytosol proteins were found to bind specifically T4 with high affinity (Ka approximately equal to 10(8)M-1) and rT3 with lower affinity (Ka approximately equal to 10(7)M-1), but they do not bind T3. The binding of both T4 and rT3 was pH dependent, however, while T4 binding had the highest values between pH 7.0 and 10, rT3 binding increased from pH 6.0 to 10.7. Divalent ions also stimulated T4 and rT3 binding. Sulfhydryl groups blocking agents such as N-ethylmaleimide (NEM) and iodoacetamide significantly decreased rT3 binding and had less profound effect on binding of T4 to cytosol proteins. The importance of free -SH groups remains unclear as dithiothreitol was found to diminish the binding of T4 and rT3.
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