Maximal number of hormonogenic iodotyrosine residues in thyroglobulin iodinated by thyroid peroxidase.
(9/3269)
Almost non-iodinated human goiter thyroglobulin has been iodinated in vitro by thyroid peroxidase to levels as high as 75 iodine atoms per mol of protein. The following results were obtained. 1. The iodine distribution obtained in vitro with human thyroglobulin strongly ressembles that obtained in vivo for rat thyroglobulin. Thus the distribution of iodine seems to depend essentially on the structure of thyroglobulin and on the reactivity of the different tyrosine residues. 2. Although the number of hormone residues increased with iodination the highest efficiency of hormone synthesis was obtained in a very narrow range of iodination: in vitro (40%) between 25 and 30 iodine atoms, and in vivo (48%) between 10 and 20 atoms. This result suggests that the tyrosines which are coupled with a high efficiency are iodinated sequentially. 3. Maximal thyroxine content was found to be lower than approximately 3 mol/mol of thyroglobulin. This result might mean that the two 12-S subunits of thyroglobulin are not identical and that one of them is able to produce 2 mol of hormone while the second only 1 mol. (+info)
Assessment of serum thyroxine binding capacity-dependent biases in free thyroxine assays.
(10/3269)
BACKGROUND: Free thyroxine (FT4) assays may exhibit biases that are related to serum T4 binding capacity (sBC). We describe two tests that can be used to assess the presence and magnitude of sBC-dependent biases in FT4 assays. METHODS: We used a direct equilibrium dialysis FT4 assay as the reference method and compared the results obtained with those of the FT4 assays under investigation, in patient sera having a wide range of sBC. We then compared the expected and observed FT4 results for sera diluted with an inert buffer. Because serum dilution causes a predictable decrease in sBC, an increasingly negative bias on progressive dilution is indicative of a sBC-dependent bias. RESULTS: The automated FT4 assay investigated (Vitros FT4) showed no demonstrable sBC-dependent bias by either test. CONCLUSION: These two tests can be used to screen for sBC-dependent biases in FT4 assays. (+info)
Assessment of thyroid hormone assays.
(11/3269)
Four techniques for estimating serum T4 and three for estimating serum T3 have been investigated and found to be satisfactory in routine use. Normal ranges for each techniques have been established. Estimation of serum T3 by the commerical kits tested appears to have a high discriminant value in the diagnosis of hyperthyroidism, although the diagnostic definition used inevitably enhances the apparent sensitivity of these techniques. Estimation of serum T4 will identify the majority of patients with symptomatic hypothyroidism. The low sensitivity of T3 in the diagnosis of thyroid failure is confirmed. (+info)
Reverse triiodothyronine, thyroid hormone, and thyrotrophin concentrations in placental cord blood.
(12/3269)
Reverse triiodothyronine (rT3), triiodothyronine (T3), thyroxine (T4), thyroxine binding globulin (TBG), and thyrotrophin (TSH) were measured in sera from placental cord blood in an unselected series of 272 deliveries. In this series the concentrations of rT3 (mean 3.33 nmol/l, 95% confidence limits 1.6--7.0 nmol/l), were log normally distributed and did not overlap the adult normal range (0.11--0.44 nmol/l). There were no correlations between the cord blood concentrations of rT3, T3, T4, and TSH. The cord serum rT3 concentration was not influenced by maturity, birth-weight, or neonatal risk factors, whereas these factors did affect the concentrations of T3, T4, AND TBG. There is no arteriovenous rT3 concentration difference across the placenta, therefore the cord rT3 reflects the systemic rT3 concentration in the baby at birth. As rT3 in the neonate largely, if not entirely, derives from thyroxine from the fetal thyroid, measurement of the cord rT3 concentration may be a good immediate screening test for neonatal hypothyroidism. (+info)
Ocular development and involution in the European cave salamander, Proteus anguinus laurenti.
(13/3269)
The anatomy and development of the eye of Proteus anguinus are described. The relationships between organogenesis of the eye in embryos and larva and its involution in the young and the adult are discussed. The availability (in breeding cultures) of a significant number of Proteus embryos (which are normally rare) allowed experimental analysis of the effects of light, xenoplastic differentiation and thyroid hormones on the development of the eye. The results of this study suggest that development and involution of the eye of Proteus are controlled by genetic factors which are not greatly influenced by environment, and one can, therefore, consider the microphthalmy of Proteus as a relict characteristic which is the result of a specific development with disturbance of the normal ontogenic process. (+info)
Comparison of mechanisms mediating uptake and efflux of thyroid hormones in the human choriocarcinoma cell line, JAR.
(14/3269)
We compared the specificities of transport mechanisms for uptake and efflux of thyroid hormones in cells of the human choriocarcinoma cell line, JAR, to determine whether triiodothyronine (T3), thyroxine (T4) and reverse T3 (rT3) are carried by the same transport mechanism. Uptake of 125I-T3, 125I-T4 and 125I-rT3 was saturable and stereospecific, but not specific for T3, T4 and rT3, as unlabelled L-stereoisomers of the thyroid hormones inhibited uptake of each of the radiolabelled hormones. Efflux of 125I-T3 was also saturable and stereospecific and was inhibited by T4 and rT3. Efflux of 125I-T4 or 125I-rT3 was, in contrast, not significantly inhibited by any of the unlabelled thyroid hormones tested. A range of compounds known to interfere with receptor-mediated thyroid hormone uptake in cells inhibited uptake of 125I-T3 and 125I-rT3, but not 125I-T4. We conclude that in JAR cells uptake and efflux of 125I-T3 are mediated by saturable and stereospecific membrane transport processes. In contrast, the uptake, but not the efflux, of 125I-T4 and 125I-rT3 is saturable and stereospecific, indicating that uptake and efflux of T4 and rT3 in JAR cells occur by different mechanisms. These results suggest that in JAR cells thyroid hormones may be transported by at least two types of transporters: a low affinity iodothyronine transporter (Michaelis constant, Km, around 1 microM) which interacts with T3, T4 and rT3, but not amino acids, and an amino acid transporter which takes up T3, but not T4 or rT3. Efflux of T4 and rT3 appears to occur by passive diffusion in these cells. (+info)
A negative iodine balance is found in healthy neonates compared with neonates with thyroid agenesis.
(15/3269)
We studied the effects of the presence or absence of the thyroid gland on the iodine metabolism and excretion in term Dutch newborns by performing a retrospective study of the urinary iodine excretion in 193 term newborns with abnormal congenital hypothyroidism screening results. Thirty-six euthyroid newborns with decreased thyroxine-binding globulin levels were compared with 157 hypothyroid patients, 54 due to thyroid agenesis and 103 due to thyroid dysgenesis. A significant difference in the urinary iodine excretion was observed between the agenesis group (mean: 28 micrograms/24 h) and the euthyroid newborns (mean: 46 micrograms/24 h, P=0.001). In conclusion, healthy, euthyroid, term newborns excreted more iodine in their urine than newborns with thyroid agenesis. These results strongly indicated the existence of a temporarily negative iodine balance: the excretion of iodine prevailed over the intake and the newborn's thyroidal iodine, stored during pregnancy, could be used for thyroxine synthesis in the postnatal period. Since healthy term neonates were able to maintain adequate plasma free thyroxine concentrations under normal TSH stimulation, the prenatally acquired iodine stores could be considered sufficiently high to compensate for the transient postnatal losses. (+info)
Thyroid hormones modulate zinc transport activity of rat intestinal and renal brush-border membrane.
(16/3269)
Thyroid hormone status influences the Zn2+ and metallothionein levels in intestine, liver, and kidney. To evaluate the impact of thyroid hormones on Zn2+ metabolism, Zn2+ uptake studies were carried out in intestinal and renal brush-border membrane vesicles (BBMV). Steady-state Zn2+ transport in intestinal and renal cortical BBMV was increased in hyperthyroid (Hyper-T) rats and decreased in the hypothyroid (Hypo-T) rats relative to euthyroid (Eu-T) rats. In both the intestinal and renal BBMV, Hyper-T rats showed a significant increase in maximal velocity compared with Eu-T and Hypo-T rats. Apparent Michaelis constant was unaltered in intestinal and renal BBMV prepared from the three groups. Fluorescence anisotropy of diphenyl hexatriene was decreased significantly in intestinal and renal brush-border membrane (BBM) isolated from Hyper-T rats compared with Hypo-T and Eu-T rats. A significant reduction in the microviscosity and transition temperature for Zn2+ uptake in intestinal and renal BBM from Hyper-T rats is in accordance with the increased fluidity of these BBMs. These findings suggest that the increased rate of Zn2+ transport in response to thyroid hormone status could be associated with either an increase in the number of Zn2+ transporters or an increase in the active transporters due to alteration in the membrane fluidity. Thus the thyroid hormone-mediated change in membrane fluidity might play an important role in modulating Zn2+ transport activity of intestinal and renal BBM. (+info)