Search Results
Search for other papers by G. G. Kwiecinski in
Google Scholar
PubMed
Search for other papers by D. A. Damassa in
Google Scholar
PubMed
Search for other papers by A. W. Gustafson in
Google Scholar
PubMed
ABSTRACT
A sex hormone-binding globulin (SHBG), which bound both oestradiol and dihydrotestosterone, was studied in the plasma of adult female little brown bats throughout the annual reproductive cycle. This protein was present at low baseline levels from September to May inclusive, months which correspond to the periods of hibernation, ovulation and early pregnancy. During the second half of pregnancy in June, SHBG levels increased 15- to 30-fold and remained increased throughout lactation and anoestrus/pro-oestrus (July–August). Although SHBG was increased during late pregnancy, the fact that levels were also high during and after lactation indicates that this protein is not specific to pregnancy. Plasma concentrations of thyroxine (T4) and the percentage binding of T4 to thyroxine-binding globulin (TBG) also showed marked seasonal variations, with T4 levels exhibiting a biphasic seasonal pattern. A major peak in plasma concentrations of T4 occurred around the time of spring arousal from hibernation and subsequent ovulation, while a second peak of lesser magnitude was measured in August, corresponding to the time of pro-oestrus and the onset of mating. The percentage binding of T4 by TBG was increased during the summer months in parallel with the increase in SHBG concentrations. Electrophoretic analysis of plasma T4 binding revealed a single peak of TBG activity throughout most of the year; however, during the early lactational period TBG was resolved as a double peak, suggesting the presence of a molecular variant during this reproductive stage.
Journal of Endocrinology (1991) 128, 63–70
Search for other papers by A. ŚLEBODZIŃSKI in
Google Scholar
PubMed
SUMMARY
(1) Experiments were performed on three litters of pigs (four animals in each litter) between birth and the 8th day (inclusive) of life.
(2) The relation between the variation in thyroxine-binding globulin (TBG) capacity and the rate of thyroxine utilization has been taken as an indication of the ability of thyroxine production to maintain a fairly constant percentage of saturation of the TBG.
(3) Dynamic changes in the interaction between the thyroid hormone and the plasma protein binding sites are shown. Changes in the binding capacity of TBG were negatively correlated with uptake of [131I]triiodothyronine by erythrocytes (r = −0·64; P < 0·01) and positively correlated with the protein-bound iodine (PBI) value (r = +0·92; P < 0·01).
(4) The value for saturation of the plasma TBG capacity was relatively stable and amounted to 67·38 ± 5·47%.
(5) The total quantity of thyroxine which has to match the variability of the protein binding site capacity was calculated to be only 13·72% of the daily production of the hormone in 8-day-old pigs.
(6) The physiological implication is discussed of changes in TBG capacity resulting in an increase of the bound-thyroxine pool in relation to the daily utilization rate of the hormone.
Search for other papers by R Vranckx in
Google Scholar
PubMed
Search for other papers by M Rouaze-Romet in
Google Scholar
PubMed
Search for other papers by L Savu in
Google Scholar
PubMed
Search for other papers by P Mechighel in
Google Scholar
PubMed
Search for other papers by M Maya in
Google Scholar
PubMed
Search for other papers by E A Nunez in
Google Scholar
PubMed
Abstract
We have investigated the role of the thyroid compared with the hypophysis in the regulation of the two saturable thyroid hormone carriers of rat serum, thyroxine-binding globulin (TBG) and transthyretin (TTR). We examined, at serum and hepatic mRNA level, the responses of TBG and TTR to thyroidectomy (Tx), hypophysectomy (Hx) and replacement treatments with tri-iodothyronine (T3) or/and GH, both hormones which are depleted when the thyroid or hypophysis are removed. The studies were performed on male rats at the age of 8 weeks, when the developmentally regulated TBG becomes undetectable after its transient postnatal rise, while the non-developmentally regulated TTR presents its normal, age-independent level of expression.
Tx-induced TBG re-expression was completely reversed by T3 replacement and unresponsive to GH replacement. TTR in the serum, on the other hand, was not affected by Tx or T3 replacement, moderately reduced by Tx in terms of the amount of mRNA, and markedly reduced by GH replacement. GH treatment, moreover, inhibited the expression of TTR in euthyroid controls. Hx, like Tx, induced TBG re-expression, an effect efficiently antagonized by T3 replacement. However, TBG synthesis was higher in Hx than in Tx rats and less effectively antagonized by T3 replacement. Most unexpectedly, GH induced a dramatic further increase in TBG synthesis, and the TBG synthesized in the GH-replaced Hx rats was entirely resistant to down-regulation by T3 replacement. TTR was markedly decreased at both serum and hepatic levels by Hx, unaffected by T3 and further decreased by GH replacement.
Our evidence is consistent with two distinct regulatory pathways for TBG, one under direct negative control by the thyroid hormones, without GH mediation, and the other independent of the thyroid, but involving GH, possibly for its role in the control of carbohydrate metabolism. We have shown that TTR depends little on the thyroid and is regulated by pituitary factors in a complex way, since it is inhibited by Hx but also by treatment with GH. The divergent regulatory pathways of TBG and TTR may be important in the homeostasis of thyroid hormone bioavailability.
Journal of Endocrinology (1994) 142, 77–84
Search for other papers by Julia N C Toews in
Google Scholar
PubMed
Search for other papers by Geoffrey L Hammond in
Google Scholar
PubMed
Search for other papers by Victor Viau in
Google Scholar
PubMed
of increased hepatic thyroxine-binding globulin (TBG) production ( Fig. 1 ). The ontogenic changes in these systems as it pertains to the HPA axis are as follows. Figure 1 Early postnatal development: androgen imprinting and HPT maturation
Search for other papers by R. L. SUTHERLAND in
Google Scholar
PubMed
Search for other papers by M. W. SIMPSON-MORGAN in
Google Scholar
PubMed
Electrophoretic studies employing a variety of media and buffer systems have repeatedly shown that tracer thyroxine (T4) moves with two distinct protein bands in sheep serum. These bands correspond to thyroxine-binding globulin (TBG) and serum albumin (Annison, 1960; Farer, Robbins, Blumberg & Rail, 1962; Refetoff, Robin & Fang, 1970). It has been pointed out by Gordon & Coutsoftides (1969) that such electrophoretic techniques are unlikely to depict closely T4 binding in vivo. For this reason we have developed a competitive-binding technique, using Sephadex G-25, which has enabled the measurement of the T4-binding properties of sheep serum proteins at physiological pH. This technique is similar in principle to that previously described by Pearlman & Crépy (1967).
Sephadex G-25 binds T4 in a highly predictable way. When a constant amount of G-25 is in contact with a constant volume of buffer, at equilibrium, the T4 present
Search for other papers by R. L. SUTHERLAND in
Google Scholar
PubMed
Search for other papers by M. W. SIMPSON-MORGAN in
Google Scholar
PubMed
The concentration of circulating plasma thyroxine (T4) appears to have little effect on the maximal binding capacity of plasma thyroxine-binding globulin (TBG). Several studies in man have shown that thyrotoxicosis results in normal or slightly lowered levels of TBG, while hypothyroidism leads to a normal or slightly increased TBG binding capacity (Oppenheimer, Squef, Surks & Hauer, 1963; Inada & Sterling, 1967; Gordon, Kleinerman, Ehrenfeld & Ehrenfeld, 1971). In contrast the binding capacities of corticosteroid-binding globulin (CBG) and sex steroid-binding globulin (SBG) have been shown to be markedly affected by the level of circulating thyroid hormone. In the rat the binding capacity of CBG was markedly depressed by thyroid-ectomy and enhanced by chronic administration of T4 (Labrie, Raynaud & Fortier, 1965). Similarly, Dray, Mowszowicz, Ledru, Crépy, Delzant & Sebaoun (1969) administered T4 to normal human subjects and observed an increase of SBG concentration. Hyperthyroidism has been shown to
Search for other papers by A. ŚLEBODZIŃSKI in
Google Scholar
PubMed
The highest level of serum free thyroxine (T4) on the first day of life occurs in the pig (Ślebodziński, 1965) and the human infant (Marks, 1965). It decreases thereafter as the result of a gradual rise in the thyroxine-binding globulin (TBG) in pigs, or in the thyroxine-binding pre-albumin fraction in infants (Van den Schrieck, 1969). An increase in the half-life of T4 in blood with a simultaneous rise in TBG in newborn calves has also been reported (Nathanielsz, 1969). Because of the physiological change in the thyroxine-binding protein, the plasma T4 level does not seem to be an adequate indicator of the peripheral utilization of the hormone in the neonatal period. In the present experiment the tri-iodothyronine-binding coefficient (T3-BC), regarded as proportional to free T4 (Gimlette, 1967), was used for assessment of variation in levels of the metabolically active form of the hormone in
Search for other papers by E. J. Cookson in
Google Scholar
PubMed
Search for other papers by M. R. Hall in
Google Scholar
PubMed
Search for other papers by J. Glover in
Google Scholar
PubMed
ABSTRACT
Antisera raised against domestic fowl transthyretin (thyroxine-binding prealbumin) and quail albumin were used to identify thyroxine-binding proteins in the plasma of White storks (Ciconia ciconia) and to measure seasonal changes in these proteins. Three plasma proteins were shown to bind thyroxine (T4). They were albumin, transthyretin and a protein with an electrophoretic mobility on non-denaturing poly-acrylamide gel electrophoresis intermediate between albumin and transthyretin. There was no thyroxine-binding globulin.
The plasma concentrations of transthyretin and albumin were measured in male and female storks exposed to the photoperiodic and climatic conditions experienced during an annual cycle at 46°N,11°E. The storks were in four age groups, fledglings and 1-, 2- and 3-year-old birds. A strong correlation (P < 0·001) was found between daylength and the concentration of transthyretin during the period from February to August in the 1-, 2- and 3-year-old male and female storks, with peak values of 150–210 mg/l in May, June and July coinciding with the annual moult. Between September and January the concentration of plasma transthyretin was low, ranging between 80 and 100 mg/l. The concentration of plasma albumin was not correlated with seasonal changes in daylength and did not change during moult. It is suggested that seasonally high concentrations of plasma transthyretin may have a physiological role in moult.
J. Endocr. (1988) 117, 75–84
Search for other papers by A. ŚLEBODZIŃSKI in
Google Scholar
PubMed
SUMMARY
(1) The interaction between thyroid hormone and thyroxine-binding globulin (TBG) has been studied in 39 pigs from eight litters, aged from 12 hr. to 11 days. In addition, single observations were made on six batches of 42 pigs from 1 day to 6 months old and in five newborn sheep.
(2) A rapid increase in the level of the unsaturated TBG capacity was found to occur from the 1st day after birth.
(3) Continuous changes in the unsaturated TBG capacity resulted in a decline in the plasma level of free thyroxine and in a decrease in the uptake of [131I]triiodothyronine by erythrocytes. Equilibrium between the hormonal iodine metabolism and its blood carrier is reached at the end of the 1st week of life.
(4) These findings suggest that in discussing thyroid metabolism in neonatal animals it is important to distinguish between the early neonatal adaptive period and the remainder of the period of thyroid hyperactivity. The physiological implications of the higher level of free thyroxine in the blood after birth for the adaptation to post-uterine life is discussed.
Search for other papers by K. Ichikawa in
Google Scholar
PubMed
Search for other papers by K. Hashizume in
Google Scholar
PubMed
Search for other papers by T. Miyamoto in
Google Scholar
PubMed
Search for other papers by Y. Nishii in
Google Scholar
PubMed
Search for other papers by K. Yamauchi in
Google Scholar
PubMed
Search for other papers by H. Ohtsuka in
Google Scholar
PubMed
Search for other papers by T. Yamada in
Google Scholar
PubMed
ABSTRACT
An aqueous two-phase partitioning study of partially purified nuclear thyroid hormone receptor from rat liver was performed. Stability of 3,5,3′-tri-iodo-l-thyronine (T3)–receptor complex and T3-binding activity in the presence of dextran or polyethylene glycol were assessed in order to determine the amount of occupied or unoccupied receptors in each phase. Partition coefficients were calculated as the ratio of receptor concentration in the upper polyethylene glycol-rich phase H2O and that in the lower dextranrich phase H2O. The partition coefficient was a sensitive function of the salt at pH above 6·1 and below 5·1. The salt had no effect on the partition coefficient at pH around 5·6. These results suggest that the isoelectric point of the thyroid hormone receptor is about 5·6, confirming previous determinations using isoelectric focusing. The partition coefficient of the receptor decreased upon T3 binding, regardless of the salt composition. In contrast, the partition coefficient of thyroxine-binding globulin increased upon T3 binding. Free T3 preferentially partitioned into the upper polyethylene glycol-rich phase and gave a partition coefficient higher than 1·0. These results strongly suggest that the decrease in the partition coefficient of the receptor upon hormone binding reflects conformational changes or changes in electrostatic properties of the receptor upon hormone binding. Such an alteration may be involved in biological activation of the receptor upon hormone binding.
J. Endocr. (1988) 119, 431–437
