Thyroidal I131 Release Research Articles

The effect of mercuric chloride on thyroid function in the rat

Oral administration of 3 mg of mercuric chloride for 6 consecutive days increases thyroid function as noted by an increase in thyroid 131I release rate. Administration of 2.5 mg of mercuric chloride daily for 40 days enhanced thyroid weight, thyroidal 125I uptake, and serum PB125I. Chromatographic analysis of thyroid pronase hydrolysates of mercury-treated rats displayed a pattern of distribution in thyroid labeling which demonstrated an increased percentage of labeled monoiodotyrosine (MIT), no alteration in percentage of labeled diiodotyrosine (DIT) or T4, but a significant reduction in percentage of labeled T3 indicating perhaps a coupling defect in synthesis of T3 exerted by mercury. Administration of mercuric chloride at 100 ppm for 3 months results in a decrease in thyroidal 131I uptake and depression in the thyroidal 131I release rate which were permanent and irreversible. These findings indicate that the influence of mercuric chloride ingestion on thyroid function probably reflects the quantity of mercuric chloride administered and the length of time during which exposure to mercury persists.

Altered thyroidal responsivity to thyrotropin induced by circulating thyroid hormones. A "short-loop" regulatory mechanism?

We studied the effect of thyroid hormone administration on responsivity of murine thyroid to exogenous thyrotropin (TSH) in order to explore the possibility that the thyroid gland might be directly inhibited by its own hormones. In the rat both L-thyroxine (T4) and 3,5,3'-L-triiodothyronine (T3) pretreatment inhibited TSH-induced thyroidal ornithine decarboxylase (ODC) activity in vivo in a dose-related manner (half-maximal inhibition, 1.7 mug/rat and 0.6 mug/rat, respectively). Other structurally related compounds exhibited the following inhibitory potencies compared to T4: T3, 283%; triiodothyroacetic acid, 40%; D-T4, 18%; 3,5-L-diiodothyronine, 9%. Monoiodotyrosine, diiodotyrosine, and iodide were not inhibitory. The full inhibitory effect of T4 or T3 was observed when thyroid hormone was administered from 96 to 12 h before TSH and was also seen in hypophysectomized animals. Pretreatment with T4 or T3 in divided doses over 2 1/2 days inhibited TSH-induced increase in [1-14C]glucose oxidation to 14C02 and [3H] leucine incorporation into protein in rat thyroid. In the mouse T4 or T3 pretreatment (0.25-25 mug daily) caused dose-related inhibition of both thyroidal ODC activity and 131I release induced by TSH in vivo. In mice on a low-iodine diet (LID) but not in animals on a regular diet (RD) NaI pretreatment also blunted TSH-induced thyroidal ODC activation and 131I release. When LID or RD mice were pretreated with 12.5-125 mug of T4 or T3 over 2 1/2 days, TSH-induced in vitro stimulation of thyroid cyclic 3',5'-adenosine monophosphate formation was inhibited in a dose-related manner; NaI pretreatment was inhibitory in the LID mouse only. Prior administration of exogenous TSH blunted the activation of thyroid ODC and thyroid hormone release induced by subsequent TSH administration in rat and mouse. These studies indicate altered thyroid responsivity to TSH under the influence of circulating thyroid hormones and suggest the existence of a "short-loop" negative feedback regulating thyroid function.

Thyrotrophin secretion from rat pituitary autografts infused with synthetic thyrotrophin releasing factor.

SUMMARY Thyroidal uptake and release of 131I were used to study the response of pituitary autografts to locally infused synthetic thyrotrophin releasing factor (TRF) and porcine median eminence extract (MEE). Thyroidal release rates of 14% 131I/24h were maintained during continuous infusion of grafts with MEE (equivalent to 4 hypothalami/day) while 12·6% 131I/24 h was lost from thyroids of rats whose pituitary autografts were infused with 1000 ng synthetic TRF/day. Infusion of autografts with 5, 50 and 250 ng synthetic TRF/day resulted in lower, but dose-dependent, thyroidal responses suggesting that synthetic TRF could induce thyrotrophin (TSH) synthesis in the grafts. At all doses of TRF, thyroidal 131I release was significantly increased by daily injection of cortisone (2 mg s.c.). Local TRF stimulation of TSH release from pituitary grafts significantly increased the dose of thyroxine (T4) needed to decrease thyroid activity, and while 1·0 μg T4/100 g depressed activity in rats receiving saline infusions, 1·7–2·7 μg T4/100 g was needed to inhibit 131I release in rats receiving 250 ng TRF/day, and 3 μg T4/100 g was needed by rats receiving 1000 ng TRF/day. Continuous TSH infusion (25–28 mu./day) into hypophysectomized rats induced thyroidal 131I release at rates similar to those in rats with TRF-stimulated pituitary autografts. It is suggested that while synthetic TRF can enhance TSH synthesis in the pituitary its effects on TSH synthesis may normally be potentiated by other humoral substances.

Intrathyroidal recycling of iodide in the rat: effects of goitrogens.

SummarySince ClO4- accelerated thyroidal 131I release in intact rats or in hypophysectomized rats treated with TSH, and since it failed to do so in T4-treated rats, it seemed that ClO4- interfered with the recycling of iodide derived from free iodotyrosines. Similarly, MTU did not increase the rate of release of 131I in T4-treated rats, but did significantly so in TSH-treated, hypophysectomized rats. It thus seemed that intrathyroidally recycling iodide was largely from free iodotyrosines produced by hydrolysis of thyroglobulin. ClO4- was similarly effective as MTU and PTU in TSH-treated hypophysectomized rats, but it was less effective in intact rats. This difference was due to the fact that more TSH was secreted in response to PTU or MTU in intact rats thus producing a large amount of iodotyrosines through the hydrolysis of thyroglobulin.

Selective breeding for variations in thyroidal iodine release rate in mice.

SUMMARY Mice were selectively bred for high and low thyroidal 131I release rates. Two lines with sharp contrast in the selection criterion were produced, and an estimate of heritability was made. There were correlated differences in thyroid histology, protein-bound 131I, cholesterol level, haematocrit, adrenal and testicular weights, and some behavioural characteristics. It was concluded that multiple genetic factors affect the rate of thyroidal iodine release, and that the high release strain had greater thyroid activity than the low release strain. Some genetic aspects of thyroid function are discussed.

Effects of Ca ++ and Mg ++ on secretion in vitro by mouse thyroid glands.

The effect of varying the concentration of medium K+ and Na+ on in vitro thyroidal 131I release was studied. Elevation of medium K+ to levels previously shown to depolarize thyroid membranes had no effect on thyroidal 131I release. A dependence of secretion on Na+ both in terms of 131I release and colloid phagocytosis was demonstrated by replacing Na+ with K+, choline, sucrose, or Tris. Oubain and K+-free medium, under conditions which inhibited membrane transport functions, inhibited 131I release and colloid droplet formation stimulated by both TSH and cyclic AMP. Thus activation of colloid phagocytosis by cyclic AMP appears to depend on medium Na+ and a functioning Na+- K+ transport system. (Endocrinology 90: 1452, 1972)

Secretion Rates of Thyroxine and Triiodothyronine in Dairy Cattle

Thyroid hormone secretion rates (TSR) were determined in 7 lactating dairy cows by the substitution method (suppression of thyroidal 131I release) and averaged .21mg L-thyroxine (L-T4) equivalents per 45.4kg body weight per day. In the same animals, TSR for thyroxine (T4SR) and for triiodothyronine (T3SR) were determined separately by the radioiodine labelled hormone pool turnover method. Pool sizes in the 7 cows were 36.9 liters (8.27% of body size) for L-T4 and 107.1 liters (22.1% of body size) for l-triiodothyronine (L-T3) when no goitrogen was given but were increased to 56.0 liters (12.2% of body size) for L-T4 and 201.0 liters (41.5% of body size) for L-T3 when the goitrogen methimazole (tapazole) was given orally at 4g per 454kg body weight per day (P<.05). Turnover rates as half-lives in days were 1.29 and .79 for L-T4 and L-T3 in the absence of goitrogen and 1.59 and 1.02 with goitrogen. Concentration of L-T4 in the plasma pool was 7.49μg per 100ml without the goitrogen and 6.18μg per 100ml with it while the concentration of L-T3 in the plasma pool, measured in the absence of goitrogen treatment only, was .149μg per 100ml. Mean T4SR in the 7 cows was .143mg per 45.4kg body weight per day without a goitrogen and .148mg in the presence of the goitrogen; T3SR was .0139mg without methimazole and .0193 with it. If L-T3 is 2.1 times as effective as L-T4 in suppressing 131I release by the thyroid, the combined TSR of L-T3 and L-T4 without a goitrogen would be .172mg of L-T4 equivalents per 45.4kg body weight per day and .189mg with the goitrogen. On this basis the substitution method overestimates TSR in cattle by 12 to 22%. Correlation coefficients for TSR with milk production were positive but low and nonsignificant, varying from .64 to zero and being .30 in 39 comparisons.

Different effects of methylmercaptoimidazole and propylthiouracil on thyroidal 131-I release in rats on ClO4.

The administration of propylthiouracil to rats is followed by a prompt increase in circulating TSH (1,2). To test further the idea that this is related to the extrathyroidal effects of PTU on l-thyroxine (l-T4), we have screened the effects of several other antithyroid drugs on TSH release. We were especially interested in those drugs, such as thiourea and methylmercaptoimidazole (MMI), known to lack extrathyroidal effects on l-T4 metabolism. The change occurring after a single injection of the drug in the rate of thyroidal 131I release of rats on ClO4− was taken as an indirect measure of a possible change in circulating TSH. Contrary to what we expected on the basis of the idea indicated above, we found that MMI behaved similarly to PTU, inasmuch as it promptly discharged 131I from the ClO4−-blocked thyroid. To see whether this similarity might be only apparent, the experiment was repeated in hypophysectomized rats on ClO4− and exogenous TSH. It was found that under such conditions PTU had no effect, whe...

Mechanism of the inhibitory effect of iodide on thyroidal 131-I release in the rat.

Mouriz et al. (1) have recently reported that KI injected after propylthiouracil (PTU) given in incompletely blocking doses increased the thyroidal synthesis of iodothyronines. They suggested that this led to enhanced secretion of thyroid hormones, and hence decreased production of TSH, which then was reflected by a decline of the previously elevated thyroidal 131I release rate. However, we have found that KI leads to a rapid reduction of thyroidal 131I release in hypophysectomized rats given TSH and 5 or 30 rag PTU daily. Depressing effects of KI on thyroidal 131I release therefore do not have to involve altered secretion of TSH. Unlike Mouriz et al. (1), we did not find that KI increased the percentage of 131I in the iodothyronine fraction of thyroid homogenates of intact rats given incompletely blocking doses of PTU, nor did it have such an effect in similarly treated hypophysectomized, TSH-injected rats. (Endocrinology 81: 643, 1967)

A Comparison of the Effects of Environmental Temperature Changes and 4.4°C. Cold on the Biological Half Life (t 1/2) of Thyroxine-I131 in Fowls

IT HAS been shown that the thyroid hormone secretion rate (TSR) of fowls is significantly lower during summer months than during winter months (Turner, 1948; Stahl and Turner, 1961). The rate of uptake and release of thyroidal-I131 has been shown to be stimulated by short term exposure of fowls to 4.4°C. However, these rates were shown to return to normal by longer term exposure to 4.4° C. (Hendrich and Turner, 1963). The thyroid stimulating hormone secretion rate (TSH-SR) of fowls has been shown to be increased by cooler as compared to warmer environmental temperatures (Hendrich and Turner, 1964).The biological half-life (t 1/2) of thyroxine-I131 (L-T4-I131) refers to the time required for the disappearance of one-half of the hormone present in the blood at a given time. The purpose of the following research was to compare the effects of environmental temperature changes and a 4.4°C. temperature on the t 1/2 …

Mechanism of the suppression by iodide of the thyroidal 131-I release rate in the rat.

Yamada et at. (1) reported that the administration of KI decreased the thyroidal 131I release rate of the rats receiving moderate doses of propylthiouracil (PTU) (5 mg/day or less) to block recycling of radioiodide. It had no effect when the rats received 30 mg PTU/day, though the half-life of thyroidal 13lI was the same in both cases. These findings are confirmed here. It is moreover shown that in the first case the injection of KI results in an increased synthesis of iodothyronines, but not in the case of rats on the higher PTU doses. Estimation of thyroidal 131I release rates, intrathyroidal 127I distribution among iodine-containing compounds, plasma PBI and plasma and pituitary TSH activities in animals receiving an injection of stable iodide while the thyroid was being blocked with C1O4- or with PTU support the following interpretations: The thyroidal 131I release rate of rats receiving either high or low doses of PTU reflects an intensely increased, and not a normal, degree of TSH stimulation (2-5)....

Alterations in thyroid physiology during pneumococcal septicemia in the rat.

The impact of acute infection on thyroid physiology was investigated in rats infected with a type-specific pneumococcus. Infected rats showed a lower thyroidal131I uptake than healthy controls at all time periods studied. Unlike in the rat, thyroidal131I uptake curves in the infected and healthy mouse and guinea pig were superimposable. Thyroidal131I release in the infected rat was significantly delayed when compared to similar release curves in uninfected animals. Although the thyroid of the infected rat responded to a physiologic dose of exogenous TSH, both its uptake and release of131I showed an absolute reduction. Serum TSH levels measured by bio-assay were not altered during infection. The disappearance time of131I-T4 from blood of infected rats was significantly shorter than that of healthy controls, while disappearance times of blood131I-T3 were unchanged. Organ radioactivity was measured following serial sacrifice after the administration of131I-T4 or 131I-T3 to healthy and infected rats. In the T...

Independence of the thyroid and adrenal gland in potassium thiocyanate (KCNS) induced hypotension in rats.

ABSTRACT KCNS administered to intact rats depressed thyroidal radioiodine (131I) uptake and accelerated thyroidal 131I release. A marked thyroidal hypertrophy was present following administration of KCNS for 16 days. The same treatment caused a sustained fall in blood pressure (BP). This hypotensive effect was not affected by thyroxine treatment, thyroidectomy, thyroidectomy plus thyroxine treatment, placement of a hypothalamic lesion, and hypophysectomy plus thyrotrophin (TSH) treatment. Pituitary-adrenal activity in KCNS-treated rats was not changed but the secretion of aldosterone appeared to be increased. A lowering of BP following KCNS treatment also occurred in adrenalectomized rats, and in adrenalectomized rats treated with corticosterone or aldosterone. Dexamethasone in adrenalectomized as well as in intact rats blocked KCNS-induced hypotension. From this study it is concluded that the lowering of BP as caused by KCNS treatment in the rat, is independent of alterations in the function of the thyroid and the adrenal gland.

Oral Effectiveness of l-Thyroxine, l-Triiodothyronine, and Thyroprotein as Compared to Injections of l-Thyroxine and Thyroprotein1,2

The thyroid hormone secretion rate (TSR) of ten nonlactating dairy cows was determined using l-thyroxine (L-T4) and thyroprotein by injection. The equivalent biological effectiveness of L-T4, l-triiodothyronine (L-T3), and thyroprotein by oral administration was then determined.When L-T4 was injected, the mean TSR was found to be 0.17 mg/100lb bw, with a range from 0.15 to 0.25 mg/100lb bw. When L-T4 was administered orally, it was found to be only 9.4% as effective as by subcutaneous injection. The doses that inhibited thyroidal I131 release ranged from 1.5 to 2.0 mg/100lb bw, with a mean of 1.83mg/100lb bw.L-T3 given orally was 21.4% as effective as injected L-T4, requiring a mean of only 0.8mg/100lb bw, with a range of 0.7 to 1.0 mg/100lb bw.Thyroprotein given orally was as effective as L-T4 given orally. Doses of thyroprotein were given to contain from 1.25 to 2.25mg L-T4/100lb bw, with a mean of 1.78 mg/100lb bw. The biological effectiveness was 9.9%, very close to the 9.4% observed for l-thyroxine.When injected subcutaneously, thyroprotein was found to be only 84.4% as effective as injected L-T4. Thyroprotein was given to equal 0.15 to 0.25mg L-T4/100lb bw, with a mean of 0.21mg L-T4/100lb bw.

Critical studies on determination of thyroid secretion rate in cold-adapted animals.

Estimation of thyroid secretion rate by determining the amount of l-thyroxine required to block the thyroidal I131 release, confirmed that the thyroxine requirement of 6 C-acclimated rats is twice as high as that of 23 C-acclimated controls (5.5 ± 0.7 μg/100 g per day against 2.73 ± 0.3 μg/100 g per day). In white rats acclimatized to cold by outdoor exposure during the winter on the other hand, it was only 1.8 ± 0.38 μg/100 g per day. Larger amounts of thyroxine were found in the feces of the 6 C-acclimated rats (1.66 ± 0.66 μg/100 g body wt per day) as compared to 0.69 ± 0.07 μg/100 g body wt per day for controls. Urinary elimination rates of I131 were more rapid in “6 C rats” than in controls. These observations indicate that the greater requirement for thyroxine in cold-adapted rats is at least partly due to greater fecal loss of the hormone. It seems plausible to seek an explanation for the lesser thyroxine requirement of the outdoor winter rats in their fecal elimination rate of that hormone. cold acclimation; fecal excretion of thyroxine Submitted on June 18, 1964

EFFECTS OF SALICYLATE AND ITS NONCALORIGENIC CONGENERS ON THE THYROIDAL RELEASE OF 131-I IN PATIENTS WITH THYROTOXICOSIS.

In contrast to the findings in a recent report, large doses of salicylate did not consistently slow the thyroidal release of 131I in patients with thyrotoxicosis. In 7 patients who received salicylate, and in 4 tests in which noncalorigenic congeners of salicylate (gentisate and gamma-resorcylate) were administered, slowing of thyroidal release of 131I was observed in only 2, and in both this change was very slight. In the remaining 9 studies, salicylate or its congeners either did not change or appeared to increase thyroidal 131I release rates. Since large therapeutic doses of 131I had been given to the patients in the previous study, it seems possible that the slowing of 131I release observed was due to an inhibition by salicylate of radiation thyroiditis. In all the patients, a decrease in the PBI occurred during the administration of salicylate or its congeners. This decrease could be ascribed largely to the selective inhibition of thyroxine binding by prealbumin which was evident in all the patients during administration of these compounds.

INFLUENCE OF THE NURSING STIMULUS UPON THYROID HORMONE SECRETION IN THE LACTATING RAT.

The influence of the nursing stimulus upon thyroid gland secretion was tested in the lactating rat during mid-lactation. Milk removal from the 6 pectoral mammary glands was prevented in all rats by galactophore ligation on postpartum day 2. Injection of 1.5 μg/100 g/day L-thyroxin was less effective in blocking thyroidal 131I release in lactating rats than in nonlactating rats. The effectiveness of the injected thyroxin in the lactating rat increased within 24 hr after the young were removed. In another experiment, a significant increase in plasma PB131I resulted from 6 hr of normal nursing of the pelvic mammary glands. No increase in plasma PB131I occurred following 6 hr of nursing of pelvic mammary glands from which milk removal was prevented by ligation of the galactophores. When the pelvic mammary glands were deprived of somatic sensory innervation by spinal cord transection and the contained milk was removed by nursing young with the aid of oxytocin injections to the mothers, the PB13lI level after 6...

STIMULATION OF THYROIDAL I 131 RELEASE IN THE DAY-OLD CHICK BY A SINGLE INJECTION OF THYROXINE OR PROPYLTHIOURACIL.

STIMULATION OF THYROIDAL I 131 RELEASE IN THE DAY-OLD CHICK BY A SINGLE INJECTION OF THYROXINE OR PROPYLTHIOURACIL.

Time Relations in the Alteration of Thyroid Gland Function in Fowls

PREVIOUS studies have shown that seasonal variations of environmental temperature affect the functional activity of the thyroid gland of fowls. Turner (1948) observed a 15% reduction in thyroxine secretion rate (TSR) of hens from March to May as the mean temperature increased.In two separate lines of New Hampshire fowls maintained in this laboratory, Stahl and Turner (1961) observed significantly higher TSR’s during the winter months than during the summer months. Stahl et al. (1961a) determined the increase in TSR of New Hampshire fowls maintained in a constant temperature chamber held at 40°F. They found that the TSR of these birds increased significantly for varying periods of time and after 190 days of subjection to 40°F., in some birds the TSR continued to increase. However, during the first 8 hours at 40°F., no change in the slope of the curve of thyroidal-I131 release was observed, indicating that the fowl’s pituitary…

Effect of propylthiouracil upon thyroidal I-131 release in the methimazole-thyroxine treated rat.

Propylthiouracil (PTU) in doses of 0.05, .15, 1 or 10 mg/day quickly accelerated the rate of thyroidal I131 release in 15 of 21 adult rats whose recycling of I131 was prevented by methimazole and whose initial thyroidal I131 release was slowed by exogenous thyroxine. The magnitude of the response was independent of PTU dose. One or 2 rats failed to respond to each dose of PTU administered. Rats whose thyroidal I131 release rates were accelerated by PTU had significantly higher plasma levels of radioactivity than rats whose thyroidal I131 release slopes were unaffected by PTU. The percentages of protein-bound I131 and inorganic I131 in the plasma, however, were unchanged. These data confirm the thesis that PTU administration promptly causes an increased thyrotrophin secretion by the pituitary.