Existence of extrathyroidal conversion inhibitor (IEC) in starved animals and its influence on thyroid hormones deiodination in liver and kidney in vitro

To find out whether an inhibitor of extrathyroidal conversion of iodothyronines is present in sera of starved animals, pig liver and kidney homogenates were incubated with T4, T3 or rT3 and dithiotreitol in the presence of evaporated diethyl ether extracts of sera obtained from fed and starved (1-12 days) rabbits. Sera extracts of short-term (1-4 days) starved rabbits caused a significant inhibition of T4 to T3 conversion (54% on day 3) and T4 to rT3 deiodination (52% on day 2) in liver homogenates. Extracts of sera from long-term (8 and 12 days) starved animals diminished only liver T4 to T3 conversion on day 8 and had no influence on liver T4 to rT3 conversion. 5'-deiodination of rT3 (to 3,3'-T2) in liver was gradually decreased by extracts of sera from animals starved during 2-12 days. Liver rT3-5-deiodination (to 3',5'-T2) was significantly impaired on day 4 and totally depressed by long-term starvation. In vitro T3 to 3,3'-T2 conversion in liver was markedly (59-103%) increased by ether extracts of sera from short-term fasted rabbits and considerably inhibited (62-72%) by long-term fasting. T4 to T3 conversion in kidney was significantly influenced by sera extracts obtained neither from short-term fasted rabbits and considerably inhibited (62-72%) by long-term fasting. T4 to T3 conversion in kidney was significantly influenced by sera extracts obtained neither from short-term nor from long-term fasted rabbits but T4-5-deiodination (to rT3) was reduced by sera extracts of short-term fasted animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of propylthiouracil on thyroid-stimulating hormone-induced alterations in iodothyronine secretion from perfused dog thyroids

The aim of this study was to see whether the inhibitory effect of propylthiouracil on thyroidal secretion of 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) could be reproduced in intensively stimulated thyroids, and to elucidate whether an increase in the fractional deiodination of thyroxine (T4) to T3 and rT3 during iodothyronine secretion might be responsible for the transient fall in the T4/T3 and T4/rT3 ratios in thyroid secretion seen in the early phase after stimulation of thyroid secretion. For this purpose T4, T3 and rT3 were measured in effluent from isolated dog thyroid lobes perfused in a non-recirculation system using a synthetic hormone free medium. 1 mmol/1 propylthiouracil induced a significant reduction in thyroid-stimulating hormone (TSH) stimulated T3 and rT3 release while the release of T4 was unaffected. This supports our previous conclusion that T4 is partially monodeiodinated to T3 and rT3 during thyroid secretion. Infusion of 1 mmol/l propylthiouracil for 30 min or 3 mmol/l propylthiouracil for 120 min did not abolish the transient fall in effluent T4/T3 and T4/rT3 induced by TSH stimulation. Thus, this phenomenon seems not to depend on intrathyroidal iodothyronine deiodinating processes.     

Tissue calmodulin levels in normal and Graves' thyroids

Calmodulin levels in normal human thyroids and Graves' disease thyroids were measured by specific radioimmunoassay in the presence of ethyleneglycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). The calmodulin levels in tissues from patients with Graves' disease treated with thionamide drugs were significantly higher than those in normal tissues from euthyroid patients with solitary cold nodules (normal: 484 +/- 50 ng/mg protein, mean +/- SE, n = 15; Graves': 901 +/- 54 ng/mg protein, n = 48, p less than 0.001). Such a rise in calmodulin levels in Graves' disease thyroids was also present even after the administration of 50 micrograms of T3 for 5 days before operation (828 +/- 137 ng/mg protein, n = 6, p less than 0.01). Calmodulin levels in Graves' disease thyroids were closely related to the cell height of follicular epithelium. Calmodulin levels in a columnar cell predominant group were significantly higher than those in a flat cell predominant or a cuboidal cell predominant group (columnar cell predominant: 1150 +/- 118 ng/mg protein, n = 13; flat cell predominant: 561 +/- 125 ng/mg protein, n = 3, p less than 0.05; cuboidal cell predominant: 596 +/- 40 ng/mg protein, n = 25, p less than 0.001). The increase in calmodulin content in Graves' disease thyroid could therefore possibly be attributed to the stimulation of the thyroid gland by the thyroid stimulating antibody. An immunofluorescence study demonstrated the presence of calmodulin immunoreactivity in the thyroid epithelial cells, particularly enriched in the apical border in the form of a granulated structure.     

Effect of hypothyroidism on pathways for iodothyronine and tryptophan uptake into rat adipocytes

Adipocytes are an important target tissue for thyroid hormone action, but little is known of the mechanisms of thyroid hormone entry into the cells. The present results show a strong interaction between transport of iodothyronines [L-thyroxine (T4), L-triiodothyronine (T3), reverse T3 (rT3)], aromatic amino acids, and the System L amino acid transport inhibitor 2-amino[2,2,1]heptane-2-carboxylic acid (BCH) in white adipocytes. System L appears to be a major pathway of iodothyronine and large neutral amino acid entry into these cells in the euthyroid state. We also demonstrate expression of the CD98hc peptide subunit of the System L transporter in adipocyte cell membranes. Experimental hypothyroidism (28-day propylthiouracil treatment) has no significant effect on System L-like transport of the amino acid tryptophan in adipocytes. In contrast, uptake of T3 and especially T4 is substantially reduced in adipocytes from hypothyroid rats, partly due to reduction of the BCH-sensitive transport component. Transport of iodothyronines and amino acids in adipocytes therefore becomes decoupled in the hypothyroid state, as occurs similarly in liver cells. This may be due to downregulation or dissociation of iodothyronine receptors from the System L transporter complex. Regulation of iodothyronine turnover in fat cells by this type of mechanism could contribute significantly to modulation of T4-T3/rT3 metabolism in the hypothyroid state.     

The effect of extrathyroidal conversion inhibitor from food-deprived animals on iodothyronines deiodination by pituitary and cerebral cortical homogenates in vitro

The influence of an inhibitor of iodothyronines' extrathyroidal conversion on T4, T3 and rT3 deiodination by adult pig pituitary and cerebral cortical homogenates has been investigated. The homogenates were incubated with T4, T3 and rT3 in the presence of 5 mM dithiothreitol and evaporated diethyl ether extracts of sera obtained from fed and starved (1-14 days) rabbits. The extracts had no influence either on T4 to T3 or on T4 to rT3 conversion in cerebral cortex. Deiodination of rT3 to 3,3'-T2 in that tissue was significantly inhibited only by the extracts of sera obtained from 4 days starved rabbits. Inner-ring deiodination of both rT3 and T3 was not changed by the extracts got from short-term (1-4 days) fasted animals but was significantly reduced by the extracts from long-term (7-14 days) food-deprived subjects. Pituitary conversion of T4 to T3 was diminished by 35% in the presence of sera extracts gained from 1-9 days fasted rabbits and by about 50% on day 14 of fasting, but only the latter change was statistically significant. Short-term fasting inhibited T4 to rT3 conversion on days 2 and 4. Both deiodinations of rT3 and 5-deiodination of T3 were affected by extracts of sera collected during long-term fasting.     

Can the type of variant albumin in familial dysalbuminemic hyperthyroxinemia be determined by measuring iodothyronines in serum?

A recent report documented the existence of three putative types of variant albumin in dysalbuminemic hyperthyroxinemia (DH) and suggested that measurement of the total concentration of three iodothyronines (T4, T3 and rT3) in serum of affected subjects could aid in their differentiation. In the present report, we describe three affected subjects from a single family which DH exhibited, in addition to increased serum total T4 levels, variable changes in the concentrations of total T3 and rT3. The concentrations of the following iodothyronines were above the normal limit: T4, T3 and rT3 in the propositus, T4 and T3 but not rT3 in her sister, and T4 but not T3 and rT3 in her mother. These differences cannot be caused by structurally different types of variant albumins, because the three subjects are members of the same family. They rather correlated with the relative abundance of the variant albumin in serum of the affected family members. Although previously reported subjects with DH always had serum T4 levels above the normal limit due to the predominantly higher affinity of the variant albumin for T4, significant increases in the concentration of serum T3 and rT3, reaching at times values above the upper normal range, have also been observed. Since a number of factors, including the relative abundance of the variant albumin, influence the concentration of iodothyronines in serum, their measurement alone cannot be used to determine the inherited type of DH.     

Thyroid hormones and their effects: a new perspective

The thyroid hormones are very hydrophobic and those that exhibit biological activity are 3',5',3,5-L-tetraiodothyronine (T4), 3',5,3-L-triiodothyronine (T3), 3',5',3-L-triiodothyronine (rT3) and 3,5',-L-diiothyronine (3,5-T2). At physiological pH, dissociation of the phenolic -OH group of these iodothyronines is an important determinant of their physical chemistry that impacts on their biological effects. When non-ionized these iodothyronines are strongly amphipathic. It is proposed that iodothyronines are normal constituents of biological membranes in vertebrates. In plasma of adult vertebrates, unbound T4 and T3 are regulated in the picomolar range whilst protein-bound T4 and T3 are maintained in the nanomolar range. The function of thyroid-hormone-binding plasma proteins is to ensure an even distrubtion throughout the body. Various iodothyronines are produced by three types of membrane-bound cellular deiodinase enzyme systems in vertebrates. The distribution of deiodinases varies between tissues and each has a distinct developmental profile. Thyroid hormones. (1) the nuclear receptor mode is especially important in the thyroid hormone axis that controls plasma and cellular levels of these hormones. (2) These hormones are strongly associated with membranes in tissues and normally rigidify these membranes. (3) They also affect the acyl composition of membrane bilayers and it is suggested that this is due to the cells responding to thyroid-hormone-induced membrane rigidificataion. Both their immediate effects on the physical state of membranes and the consequent changes in membrane composition result in several other thyroid hormone effects. Effects on metabolism may be due primarily to membrane acyl changes. There are other actions of thyroid hormones involving membrane receptors and influences on cellular interactions with the extracellulara matrix. The effects of thyroid hormones are reviewed and appear to b combinations of these various modes of action. During development, vertebrates show a surge in T4 and other thyroid hormones, as well as distinctive profiles in the appearance of the deiodinase enzymes and nuclear receptors. Evidence from the use of analogues supports multiple modes of action. Re-examination of data from th early 1960s supports a membrane action. Findings from receptor 'knockout' mice supports an important role for receptors in the development of the thyroid axis. These iodothyronines may be better thought of as 'vitamone'-like molecules than traditional hormonal messengers.     

rT3 production in normal man, assessed from variations in serum rT3 during short-term rT3 infusion.

The metabolic clearance rate (MCR) of 3,3'5'-triiodothyronine (reverse T3, rT3) was estimated in normal human subjects by a modified noncompartmental method using the integrated increase in serum rT3 following intravenous infusion of 0.10 nmol/min rT3 for 4 hr. The MCR-rT3 was calculated to be 102.8 +/- 17.01/day and the daily rT3 disposal to be 33.0 +/- 9.5 nmol (mean +/- SD, n = 6). The MCR-rT3 compares well to that of previous studies employing tracer kinetic methods. The disposal rate of rT3 estimated in the present study is considerably lower than found in some previous studies. The discrepancy is due to differences in the measured levels of serum rT3 in normal subjects.     

The effect of adrenaline pretreatment on the in vitro generation of 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine (reverse T3) in rat liver preparation

The effects of adrenaline (A) on liver T3 and rT3 neogenesis from T4 were studied in Wistar rats. The animals were implanted subcutaneously either with A or placebo (P) especially coated tablets which linearly released the hormone. The serum A values 6 hrs after implantation of 7.5, 15.0 and 45.0 mg tablets were 6.5 +/- 1.31, 6.8 +/- 1.8 and 16.4 +/- 1.9 ng/ml, respectively vs 4.4 +/- 2.5 ng/ml seen in P pretreated group. The output rates of A were 0.11 (7.5 mg), 0.18 (15 mg) and 0.52 microgram/ml (45 mg). The pretreatment with A led to hyperglycemia and the "low T3 syndrome". Neogenesis of T3 from T4 in medium containing liver microsomes of P pretreated rats was 5.49 +/- 0.25 pmol of T3/mg protein/min and decreased in A pretreated rats to 3.82 +/- 0.17, 3.12 +/- 0.27 and 3.06 +/- 0.11 pmol of T3/mg of protein/min. Neogenesis of rT3 from T4 in microsomes from P group was 1.52 +/- 0.09 pmol rT3/mg protein/min and increased after A to 2.71 +/- 0.11, 2.60 +/- 0.21 and 2.21 +/- 0.34 pmol of rT3/mg protein/min thus showing no dose dependency. Enrichment of microsomes medium with cytosol either from P or A pretreated rats had no effect on T3 generation thus excluding effect of A on cytosolic cofactor. Although cytosol further increased rT3 neogenesis this was seen regardless of whether cytosol was obtained from A or P implanted rats. It is concluded that A decreases the activity of T4-5'-deiodinase in liver, and possibly increases the activity of T4-5-deiodinase.     

Effect of iopanoic acid on basal and thyrotropin-stimulated thyroid hormone levels in suckling rat pups

We proposed that basal and thyrotropin (TSH)-stimulated thyroid hormone levels of rat pups would be altered in the presence of iopanoic acid (IA), a radiographic contrast agent which competitively inhibits T4-to-T3 conversion, and that the nature of these changes would further depend upon the route of TSH administration in a manner distinct from that reported in adults. To test this hypothesis, litters from 24 Sprague-Dawley female rats were adjusted to 8 pups each. On day 5, 80 pups received IA (2.5 mg/100 g body weight) injections. On day 8, control and IA pups were further subdivided, and given bovine TSH (bTSH) either by subcutaneous injection or by intragastric gavage (to simulate milk-borne TSH intake), and then sacrificed 0, 1.5, or 3 hours later. We found significantly higher T4 and reverse-T3 (rT3) levels in IA-treated pups, but IA had no effect on basal or TSH-stimulated T3 levels attained, regardless of route of bTSH administration or time post-treatment. Our data demonstrate that the effects of IA on T4 and rT3 levels in the immature rat are comparable to those observed in adult rats and humans, but that the marked depression of T3 levels found in IA-treated adults does not occur in the 8-day old rat pup. We speculate that the IA-treated suckling pup's ability to sustain normal basal T3 levels and generate elevated T3 concentrations in response to TSH stimulation may reflect the activity during development of a T4-5'-deiodinase relatively resistant to competitive inhibition by this drug.     

Placental outer and inner ring monodeiodination of thyroxine and triiodothyronines in the rabbit

Both inner- and outer-ring iodothyronines deiodinating activity was found in homogenates of rabbit placentas. The T4 to rT3 and T3 to 3,3'-T2 deiodinating activity was already high on day 10 before delivery but decreased being about 7 times lowered on day 5. Once the T3 to 3,3'-T2 monodeiodination reached a low and a relatively steady level, the outer ring deiodination of T4 begun, reaching a peak value at about day 3 before term and then fell again. The fetal serum thyroid hormones levels were low, showing no significant variability during the period of observation. The results suggested that in the rabbit, representing animals in which the thyroid gland activity begins early in fetal life, there are two distinct phases of the placental monodeiodinating activity. The first is characterized by a high inner-ring deiodinating activity (yielding rT3) and is followed by the second phase with a high outer-ring deiodinating activity (yielding T3) declining just before term.     

Low serum reverse T3 levels in patients with primary hyperparathyroidism

Although patients with primary hyperparathyroidism (1 degree HPT) were euthyroid, we measured serum thyroid hormone levels in 16 patients with 1 degree HPT together with 17 patients with hypercalcemia due to malignant diseases (HCM). In patients with 1 degree HPT, serum levels of T3, T4 and T3U were within normal range, but serum rT3 (reverse T3) levels (205 +/- 37 pg/ml, mean +/- SD) were significantly decreased as compared with those in normal controls (276 +/- 44 pg/ml, P less than 0.01). A significant inverse correlation was observed between the serum levels of rT3 and parathyroid hormone (PTH) (r = 0.54, P less than 0.05). After parathyroidectomy, serum rT3 levels were significantly elevated (240 +/- 56 pg/ml) compared to preoperative levels (P less than 0.01). Low levels of serum rT3 seemed to be attributed to the high levels of serum PTH. On the other hand, serum levels of T3 and T4 were low and serum rT3 levels were high in patients with HCM. Low serum rT3 allows for the differentiation of patients with 1 degree HPT from those with HCM.     

The relationship between basal metabolic rate (BMR) and concentrations of plasma thyroid hormones in fasting cockerels

A correlation between the Basal Metabolic Rate (BMR) and the level of rT3, and occasionally between BMR and T3 or T4 was found in 12 month fasting cockerels. The birds were fasted for 48 hrs and BMR was measured eight times (before fasting, at 6, 12, 24, 30, 36, and 48 hrs of fasting, and 4 hours after fasting). Blood samples for plasma collection were taken immediately after measuring the BMR. During starvation a decrease in BMR was observed. After refeeding BMR returned to the starting level. The decrease in BMR was accompanied by an increase in rT3 and T4 plasma levels. Between BMR and levels of T4 and rT3 negative coefficients of correlation were observed (r = -0.20 and r = -0.42, respectively). Contrary to this, the T3 level declined and was correlated with BMR (r = 0.62). After refeeding, the T3 level rapidly increased against the control value. Moreover, a high coefficient of correlation (r = -0.39) was found between the level of T3 and rT3. The data show that the reduction in plasma T3 level and increase in the rT3 one during starvation may be due to inhibition of deiodination of T4 to T3, since rT3 is a competitive inhibitor of this reaction. The presented results support the suggestion that in birds T3 is the metabolically active thyroid hormone, and rT3 antagonizes this effect.     

Differential T4 degradation pathways in young patients with preterminal and terminal renal failure.

INTRODUCTION: The aim of this study is to analyze thyroid hormone parameters in large homogenous patient cohorts with preterminal (stage 4) and terminal (stage 5) renal failure in an area of low iodine intake. PATIENTS AND METHODS: Thyroid parameters were measured in healthy controls (n=48), patients with preterminal renal failure (n=48) and patients with terminal renal failure undergoing hemodialysis (n=288). All patients were assessed by measurement of TSH, T4, T3, fT4, rT3, Tg and TPO-antibodies. RESULTS: There was a significant decrease of T4 and fT4 from healthy controls to patients with preterminal renal failure and to patients with terminal renal failure. T3 showed a decrease from healthy controls to patients with preterminal renal failure and to patients with terminal renal failure (1.54+/-0.06 microg/l VS. 1.05+/-0.05 microg/l VS. 1.09+/-0.23 microg/l, p<0.001 VS. controls). rT3 was significantly decreased in patients with terminal renal failure (0.24+/-0.01 microg/l VS. 0.25+/-0.02 microg/l VS. 0.16+/-0.01 microg/l, p<0.001). The rT3/T3 ratio was significantly elevated in patients with preterminal renal failure (p<0.01). TSH concentrations were in the normal range in all groups. CONCLUSION: Our data suggest different T4 degradation pathways in patients with preterminal and terminal renal failure.     

Measurement of thyroid hormone concentrations in human placenta

Concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) in the placenta were measured in 7 patients with abortion, in 9 patients with premature delivery, in 16 normal pregnancies and in 4 pregnant women with Graves' disease. The placentas, obtained at delivery, were homogenized and centrifuged at 800 X g. T4, T3 and rT3 concentrations in the supernatants were extracted with 3 vol. of 99% ethanol and measured by RIAs. In normal pregnancy, placental T4, T3 and rT3 concentrations were 18.8 +/- 5.9 (mean +/- SD), 0.026 +/- 0.012, and 1.70 +/- 0.49 ng/g tissue, respectively. Ratios of rT3/T3 and rT3/T4 in the placenta were about 12 and 2.3 times as high as those in the fetal sera, respectively. There was a significant positive correlation between the placental T4 and the maternal or cord serum T4 concentrations. However, no correlation was found between the placental T3 or rT3 concentrations and the maternal or cord T3 or rT3 concentrations. In 4 patients with Graves' disease, the placental T4 concentration was elevated. These results indicate that the placental T4 concentration is influenced by both the maternal and fetal serum T4, and elevated ratios of rT3/T3 and rT3/T4 in the placenta might be due to the active placental 5-monodeiodination.     

Manganese ion as a goitrogen in the female mouse

Effect of excessive ingestion of manganese (Mn) on the mouse thyroid was assessed under the conditions of normal intake of iodide. Female mouse thyroids were enlarged after 7 weeks of administration of 200 mg/l MnCl2 X 4H2O in drinking water; 2.74 +/- 0.25 mg for control (N = 56), and 3.31 +/- 0.28 mg for Mn-treated group (N = 85) (p less than 0.001). In contrast, male mouse thyroids never became goitrous following this treatment. Manganese was goitrogenic to the castrated male mouse, but it had no effect on the testosterone-treated castrated male mouse, indicating the involvement of androgen in goiter formation. Oral administration of Mn did not severely affect blocked T/S of 125I or iodine metabolism in the thyroid. A morphological study, however, revealed that the epithelial cell in the Mn-treated mouse thyroid became flatter than that of the control. The lumens were filed with colloid in Mn-treated female mouse thyroid. The serum levels of thyroxine (T4), but not triiodothyronine (T3), were slightly reduced by Mn. These informations suggest that Mn can be a mild goitrogen for the female mouse and that the etiology of goiter formation can be interpreted by retention of colloid in the lumen.     

Effects of the infusion of glucagon on the blood levels of thyroid hormones

We have attempted to determine if mild hyperglucagonemia induced by exogenous glucagon infusion induces changes of serum thyroid hormone levels. Eleven healthy subjects, overnight fasting, received glucagon infusion (2 mg/90 min i.v.), whereas 5 healthy subjects (control group) received normal saline infusion. In the subjects infused with exogenous glucagon plasma glucagon concentrations increased from 130 +/- 24 pg/ml to 550 +/- 68 pg/ml at the end of infusion. At the same time no significant changes in serum T3, rT3 and T4 levels were found. A significant increase in serum rT3 levels was found 270 min after glucagon infusion withdrawal, whereas serum T4 levels remained unaltered during the whole period. Normal saline infusion failed to induce any variation in control group, however a late (at 6th hour) mild increase of serum rT3 in these subjects resulted comparable to the same increase of glucagon infused subjects. The results from this study suggest that mild increase in plasma glucagonemia, as found in patients with severe illness, does not induce a short-time significant lowering of serum T3 and a simultaneous rise of serum rT3 in normal subjects.     

Simultaneous observations of iodothyronine content in the thyroid gland, serum and thyroxine 5'- and 5-monodeiodinase activity in liver, during the neonatal period of the pig

Serum T4 and rT3 were high at about 4-12 h after birth, then they decreased to a nadir on day 3 (rT3) and day 7 (T4). Serum T3 concentration fell immediately after birth but then increased to a relatively stable level during the next 2-6 weeks, then fell after weaning. Reciprocal concentration profiles of T4, T3 and rT3 in the thyroid were found. The thyroidal iodothyronine content increased significantly after weaning. In the liver, 5'-monodeiodinating activity, low after birth, rose until day 3 and then decreased concomitantly with T3 in serum. The 5-monodeiodinating activity, high at birth, fell to a nadir at about 3 weeks. No changes in 5- and 5'-deiodinase activity after 3 weeks were observed. Opposite to the variations in absolute content, the iodothyronine relative proportion in thyroid tissue was practically unchanged until weaning time (6 weeks), when they rose. Serum T3/T4 and rT3/T4 ratios increased with age until weaning. The post-weaned pigs had T3/T4 and rT3/T4 ratios about two times smaller than 6-weeks-old pigs. Serum rT3/T3, high after birth, decreased with age. Summarizing, the results indicate that neither changes in the thyroid iodothyronine content nor in the liver T4-monodeiodinating activity can solely account for variations in serum TH during the early neonatal period in the pig. It is suggested that the rapid variations in serum TH levels can reflect changes in the thyroidal secretory activity in preferential T3 secretion and/or blood disappearance rates.     

Presence of triiodothyronine, no detectable thyroxine and reverse triiodothyronine in human milk.

Thyroxine (T4), triiodothyronine (T3) and reverse triodothyronine (rT3) concentrations in human milk were measured by radioimmunoassay in 114 samples obtained from 1 week to 8 months postpartum. Several assay systems applied for the determination of serum thyroid hormone concentration were proved to be unsuitable for human milk, and the method of separating free and antibody-bound hormone by polyethylene glycol was also inappropriate for milk specimens, which tended to give a falsely high value. The binding of finity of T4 to milk was lower than that to serum protein, on which 8-anilino-1-naphthalene sulfonic acid showed no remarkable effect. In spite of the high sensitivity of 100 pg/tub in T4 assay system, no immunoassayable T4 was detected in all samples with or without ethanol extraction and trypsin hydrolysates of milk. In contrast, T3 was present in a measurable amount in most of the samples, the mean +/- SD value of which was 10 +/- 9 ng/100 ml, and those in colostrum were significantly higher than those in matured milk (P less than 0.01), whereas rT3 was not detectable in 76 samples tested. These results indicate that permeability of thyroid hormones through the mammary gland is different between T4 and T3 as well as in placental transport, and human milk can not be a source of thyroxine supply for the breast-fed infant.     

The effect of iodothyronines on the conversion of thyroxine into 3,3''-5-tri-iodothyronine in isolated rat renal tubules.

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.