Thyroidal I131 Release Research Articles

Studies on inhibition of corticotropin and thyrotropin release utilizing microinjections into the pituitary.

The corticotropin-suppressing effects of dexamethasone-21-phosphate given by 2 routes of administration, systemic and intrapituitary, were compared in rats. Direct pituitary injection of dexamethasone in amounts ranging from 10 to 400 μg/kg was no more effective in suppressing adrenal venous corticosterone secretion than an equal amount administered subcutaneously. The findings were extended to include a group of animals pre-tested with a systemically ineffective amount of thyroxine injected into the pituitary. Animals showing suppression of the thyroidal I131 release rate in response to this treatment were also studied with respect to the corticotropin-suppressing effects of dexamethasone injected into the same site. Again, the intrapituitary dexamethasone injections proved to be no more effective than systemic dexamethasone injections. The observations suggest that thyroxine and adrenal steroids may act in different sites to produce suppression of their respective tropic hormones.

Methimazole: a goitrogen without apparent extrathyroidal effects in the rat.

Injection of 1.0 μg/100 g per day of l-thyroxine 1) prevented methimazole (Tapazole)-induced goiter in adult female rats without altering plasma PBI and 2) blocked thyroidal I131 release equally well in the presence or the absence of methimazole. The goitrogen did not alter the rate of degradation of labeled l-thyroxine, as manifested by urinary and fecal excretions of radioactivity. The data suggest that methimazole influences thyrotropin-thyroid hormone interplay without complicating effects of an extrathyroidal nature.

Effects of estrogen upon thyroidal I-131 relese and excretion of thyroxine in ovariectomized rats.

Estradiol benzoate (1.5 μg/100 g) increased the amount of exogenous l-thyroxine necessary to prevent thyroidal I131 release in ovariectomized rats. This effect was not mediated by a direct action on the thyroid gland since estradiol failed to evoke discharge of thyroidal I131 when thyrotropin was totally suppressed by exogenous thyroxine, whereas marked acceleration of thyroidal I131 release occurred during partial thyrotropin suppression. Daily administration of the same level of estradiol for 4 weeks to ovariectomized rats significantly increased 24- and 48- hour urinary and fecal excretions of radioactivity following a single administration of I131 l-thyroxine, without significantly altering serum PBI or thyroid weight. These data suggest that estrogen, in the proper dosage, may stimulate the rate of thyroxine secretion by the thyroid gland while also increasing its rate of degradation by the organism.

Effect of Changes in Forage Ration on the Thyroidal I131 Release Rates of Young Dairy Animals

Summary Previous reports showed that a sharp decline in milk production following certain forage ration changes could not always be explained on the basis of reduced feed intake and digestibility, or both. In one experiment the thyroidal I 131 release rates of six Holstein heifers were significantly higher shortly after they were changed to legume-grass silage than when they were fed alfalfa hay. In subsequent experiments the thyroidal I 131 release rates were significantly higher when the heifers were fed legume-grass silage from a plastic-covered stack or mixed grass-clover-alfalfa hay than when they were fed legume-grass silage from a tower silo. When the forage was changed from alfalfa hay to legume-grass silage during the time I 131 release rate was being determined, three of five calves exhibited an increased release rate, whereas their controls showed no change. When reutilization of iodine was blocked with thiouracil, the two calves switched to silage showed a significant increase in I 131 release rate, whereas one control calf exhibited a decrease and the other an increase. These changes in I 131 release rate indicated that some as yet unidentified factor(s) in certain forages exerts an influence on the thyroid activity, so that an adjustment in thyroid activity of the animal is induced when a sudden change in forage rations is made. It is suggested that changes in thyroid activity associated with changes in forage ration, at least in part, may explain the sharp decline in milk production observed when similar ration changes were made in previous experiments.

A New Procedure for Estimating Thyroxine Secretion Rate with Radioiodine

An improved technique for the in vivo estimation of thyroxine secretion rate using radioiodine is described and is compared with other techniques reported previously. The daily secretion rate is estimated as that amount of L-thyroxine which inhibits thiouracil- induced acceleration of I131 release from the thyroid gland and returns the retention of thyroidal-I131 to the rate before the start of thiouracil administration. This value is about 60 % of that obtained using an assay based on complete inhibition of thyroidal-I131 release by the injection of thyroxine in thiouraciltreated chickens, 85 % of that obtained using the same procedure with non-thiouraciltreated chickens, and close to the value derived from the goiter-prevention assay. Thyroxine secretion rates estimated by the new technique and expressed as μg L-thyroxine/100 g body weight are 1.50–1.80 for 6 to 7-weekold cockerels, and 0.58 for 12-month-old hens. The secretion rates estimated by the present partial inhibition assay of I131 release and by the goiter-prevention assay may be close to the normal secretion rate, because in both assays the exogenous thyroxine dose maintains the normal level of secretion of TSH. The other 2 kinds of assays, which are based on the assumption that exogenous thyroxine dose which completely blocks the pituitary TSH secretion is equivalent to the normal thyroxine secretion rate, yield higher estimates of the daily thyroxine secretion rate.

Biological activity of 3,3',5'-triiodo-DL-thyronine.

Experiments have been conducted to evaluate the thyromimetic activity of 3,3′,5′-triiodo-DL-thyronine in rats as determined by its ability to slow the rate of loss of thyroidal radioactivity after administration of I131 and its suppression of thyroidal 24-hour I131 uptake. The administration of this substance in doses up to five times that of L-thyroxine failed to change the thyroidal I131 release rate under conditions in which the latter compound was strongly inhibitory. Similar results were obtained whether or not the recirculation of I131 was blocked by the administration of methimazole. In suppressing thyroidal I131 uptake it appeared to have 75% the activity of thyroxine, but inorganic iodide in comparable doses was observed to be equally effective. These results are interpeted as demonstrating a lack of significant thyromimetic activity in this compound, less than 10% that of thyroxine.

350 Parathyroid Hormone and the Placental Barrier

Thyroid hormone secretion rates (TSR) were determined in 7 lactating dairy cows by the substitution method (suppression of thyroidal 131I release) and averaged .21 mg L-thyroxine (L-T4) equivalents per 45.4 kg 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 4 g per 454 kg 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 7.49 μg per 100 ml without the goitrogen and 6.18 μg per 100 ml with it while the concentration of L-T3 in the plasma pool, measured in the absence of goitrogen treatment only, was .149 μg per 100 ml. Mean T4SR in the 7 cows was .143 mg per 45.4 kg body weight per day without a goitrogen and .148 mg in the presence of the goitrogen; T3SR was .0139 mg 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 .172 mg of L-T4 equivalents per 45.4 kg body weight per day and .189 mg 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.

Comparative abilities of thyroxine and triiodothyronine as inhibitors of pituitary thyrotropin secretion in cattle

A technique is described using radioactiveiodine (I131) and the goitrogen, Tapazole, in mature dairy cows, to compare the relative biological activity of l-thyroxine (T4) and l-triiodothyronine (T3) in individual animals to inhibit pituitary thyrotropin (TSH) release and, in turn, release of thyroidal-I131. The minimal amount of either hormone required is considered the equivalent T4 or T3 secretion rate. The individuals of the Holstein breed showed a mean molar relation of 1:2.5, which was significantly higher than the means of the other breeds. The mean of 22 animals showed a ratio of 1:2.14, indicating that T3 is slightly over twice as effective as T4 in blocking TSH and thyroidal-I131 release. While T3 is more potent in blocking TSH discharge, it was observed that upon withdrawal of T4 and T3 the resumption of thyroidal-I131 release was more rapid after T3 administration.

Effects of Thiouracil Level and Pen Position on Thyroxine Secretion Rate Determined by I131 Assay

THE recent use of radioactive iodine (I131) in thyroid secretion rate (TSR) studies has constituted a significant advance in the field of thyroid physiology. Potential applications in poultry research are numerous, and some investigators have already started to exploit these (Premachandra et al., 1958; Mueller and Amezcua, 1959; Mellen and Wentworth, 1960).Pipes et al. (1958) have called attention to the complicating effect of “recycled” I131 on apparent release rate of thyroidal I131, pointing out that some of the inorganic I131 available from metabolized thyroid hormone again reaches the thyroids and can be re-incorporated into thyroglobulin. In chickens, this re-utilization of I131 occurs to such an extent that TSR estimates (based on calculation of the exogenous thyroxine dose which blocks further release of thyroidal I131) are difficult or impossible unless an antithyroid drug such as thiouracil is administered. As Pipes et al. (1958) state: “It is not necessary to completely …

Time study of acute cold-induced acceleration of thyroidal I 131 release in the hamster.

SummaryAnalysis of time sequence in pituitary and thyroid phenomena involved during acute response of hamsters to cold exposure indicates a rapidly activated neural component. Within 0.5-1 hour after cold, sensory perception of this temperature change has generated sufficient input into hypothalamic effector mechanisms to deplete pituitary TSH by 60%. After a latent period of 1.5 hours, accelerated release begins and results in 25-30% decrease of thyroidal I131 during 12 hours of cold. Thyroxine (10 μg) is capable of inhibiting thyroidal I131 release when administered as long as 2-3 hours after exposure to cold.

Reserpine and thyroid activity in fowls.

SummaryReserpine at levels of 30 μg/100 g/day and above depressed thyroidal-I131 release rate in chickens and caused body weight losses. At 15 and 30 μg/100 g/day, thyroxine secretion rate (TSR) was reduced in pigeons with depression in body weight and feed intake. No level of reserpine was found which would inhibit TSR without depressing feed intake. It is suggested that depression of thyroid activity at higher levels of reserpine is secondary to depression in food intake.

Studies on the “Feed-back Relation of Pituitary-thyroid Axis”

In the present study, the effect of thyroid hormone on the release of I131 from the thyroid gland was investigated to evaluate the “Feed-back relation of pituitary-thyroid axis.” The results were summarized as follows.Experimental studies : In normal rabbits, the release of thyroidal I131 was promptly and completely inhibited by a single subcutaneous injection of L-thyroxine (T4) (50μg or 100μg) or 3, 5, 3 triiodo-L-thyronine (T3) (10μg or 50μg).However, the same animals showed no marked inhibition following administration of KI in doses equivalent to the iodine contents of T4.Following administration of TSH (10-30 Ms.E. every twelve hours for one day), the rate of release of thyroidal I131 was increased to similar level that was seen in normal, even in animals of which the I131 release had been inhibited by T4 injection.The release of thyroidal I131 in the hypophysectomized rabbit maintained with TSH administration (5 Ms. E. every twelve hours) showed no marked inhibition by T4 injection.The release of thyroidal I131 in the adrenectomized rabbit maintained with cortisone (0.5-1mg daily) showed marked inhibition by T4 injection, as was observed in normal animal.From these data, it may be concluded that the inhibitory effect of T4 upon the release of thyroidal I131 was chiefly due to the suppression of endogenous TSH secretion.Clinical studies : In normal subjects, a single subcutaneous injection of T4 (1 or 3 mg) caused complete inhibition of the release of thyroidal I131 and increase of PBI level. On the contrary, most patients with hyperthyroidism, even in euthyroid stage, failed to show the inhibitory action of T4 on the release of thyroidal I131In normal subjects who showed an increase of PBI more than about 2μg/dl twenty-four hours after T4 administration, the percent change of the release rate of thyroidal I131 was found to be snore than about 60%, independent of the amount of increase in PBI. Whereas the percent change of the release rate of thyroidal I131 in hyperthyroid patients who showed a relatively small increase of PBI after T4 administration, was found to be less than those of normal subjects with the same amount of increase in PBI. In hyperthyroid patients who showd a larger increase of PBI, the percent change of the release rate of thyroidal I131 was correlated to the amount of increase in PBI, except a few cases (r=+ 0.50, P<0.02).From these data, it was demonstrated that the mesurements of the release rate of thyroidal I131 and of PBI after T4 administration were very excellent aids to evaluate the “Feed-back relation” (Feed-back test).In addition to this test (Feed-back test), other thyroidal function tests were also studied in most cases.As no correlation was found among the “Feed-back index” (the ratio of percent change of release rate of thyroidal I131 to increase amount of PBI), PBI, BMR, I131-uptake and exophthalmometry, these items seemed to show different aspects of thyroidal function.By summarizing these data of the “Feed-back test, ” serum TSH level and TSH-test, the author presented a hypothetical schema of the “Feed-back relation of pituitary-thyroid axis” in hyperthyroidism.

Measurement of thyroid secretion rate of individual pigeons.

A method is described in which, by the use of radioiodine techniques, thyroid function of unanaesthetized pigeons was studied. Maximum accumulation of I131 in the pigeon thyroid was accomplished within 24 hours or less followed by rapid thyroidal-I131 release. (Average biological half-life of 2.73 ± .3 days.) Estimation of thyroid secretion rate (TSR) was then made for each pigeon by injecting graded doses of l-thyroxine until the level was reached which suppressed thyrotropic hormone secretion and thus prevented further thyroidal-I131 output. Individual TSR ranged from 1.0–2.5 µg/100 gm/day with an average for 35 adult common pigeons of 1.94 ± .07 µg/100 gm/day l-thyroxine. Analyses of correlation coefficients indicated a significant negative correlation existed between TSR and biological half-life of thyroidal-I131. Nonsignificant correlations existed between TSR and 24-hour I131 uptake and between TSR and body weight. The level of thyroid hormone secretion did not influence the pigeons' crop-sac response to standard lactogenic hormone.

A mode of action for thyroid inhibition by reserpine.

SummaryReserpine had no significant effect upon thyroidal-I131 release rate resulting from injections of thyrotropin (TSH) into young mature female rats whose endogenous secretion of TSH was effectively blocked with thyroxine. In another experiment, reserpine prevented thyroid enlargement which normally results from administration of the goitrogen tapazole. Injections of tapazole and/or reserpine did not significantly affect pituitary or adrenal weight. It appears reserpine inhibits thyroid function in the rat through suppression of TSH secretion.

Effect of di-ethyl ether anesthesia on thyroid function of rats: pituitary, adrenal and thyroid relationship.

The possible role of the pituitary and adrenal hormones in the depressive effect of ether anesthesia on thyroid function in rats was studied. Di-ethyl ether anesthesia for two hours significantly depressed release of radioiodine (I131) from the thiouracil blocked thyroid gland in both bilateral adrenalectomized rats maintained with cortisone and in the bilateral adrenal-medullectomized rats. Administration of ether anesthesia depressed thyroidal uptake of radioiodine in the hypophysectomized rats treated with small doses of exogenous TSH, although no significant effect was noted inthe absence of thyrotropin. Ether anesthesia inhibited the TSH-stimulated release of thyroidal I131 in the hypophyscctomized rats. Recovery from this inhibition by ether was rapid and more marked when larger amounts of TSH were used. These findings indicate that the effect of di-ethyl ether anesthesia in rat thyroid was not mediated through the adrenal cortex or medulla. It is suggested that the ether anesthesia might influence ...

Effect of growth hormone upon thyroid secretion rate in the rat.

SummaryThe effect of 1 mg/day GH upon thyroid activity has been studied in non-lactating and lactating rats. GH did not alter thyroid secretion (TSR) or affect rate of release of thyroidal I131 in non-lactating rats though body weight was increased 2 g/day. During days 8–16 of lactation, the average TSR of 2.9 μg/100 g L-thyroxine for lactating rats receiving GH was significantly greater than the 2.2 μg/100 g obtained for untreated lactating rats. Rate of release of thyroidal I131 also was significantly increased suggesting GH in some manner effects an increase in output of TSH or thyroid hormones in the lactating rat.

Evidence of central nervous system influence upon cold-induced acceleration of thyroidal I 131 release.

During the initial 12 hours of cold-exposure (5°C) of the hamster, thyroidal I131 release is accelerated markedly. Bilateral nephrectomy, adrenal demedullectomy or adrenalectomy do not influence this response. Treatment of animals with reserpine, placement of appropriate median eminence lesions 24 hours before exposure, or chronic lesions (3–6 weeks) do not interfere with subsequent normal hormone delivery but do block the accelerated release attendant upon cold exposure. Using hypophysectomized hamsters, I131 uptake is restored to normal by treatment with TSH. After this uptake is achieved and exogenous TSH discontinued, release from the thyroid is slow and cannot be accelerated by cold. Transplantation of fragments of 1/2–2 pituitary glands into the cheek pouch of hypophysectomized hamsters temporarily restores both uptake and release. Cold-exposure, however, does not accelerate thyroidal release in such graft-bearing animals. These experiments indicate that upon cold-exposure a central nervous system stimulus is responsible for triggering the pituitary-thyroid system and that the accelerated thyroidal I131 delivery, depending upon increased secretion of TSH, requires adenohypophyseal tissue with its normal anatomical connections to the hypothalamus.

Role of pituitary, adrenal and kidney in several thyroid responses of cold-exposed hamsters.

The role of the pituitary, adrenal and kidney was investigated in several of the thyroid responses to acute and chronic cold exposure. The pituitary gland is necessary for: a) maintenance of normal thyroid weight, histology and I131 uptake in hamsters housed at room temperature; b) survival of cold-exposed hamsters; and c) the increased thyroid I131 uptake occurring during cold exposure. The initial effects of cold exposure evoke a brief period of accelerated release of thyroidal I131 followed by complete inhibition of release Also during the period of initial cold exposure, I131 uptake is sharply depressed, probably because of an increase in renal elimination of iodide. This renal mechanism is independent of the adrenal glands but appears to require the presence of the pituitary.