Dose Of TSH Research Articles

Stimulation by prostaglandin E-1 of endocytosis and glucose oxidation in canine thyroid slices.

Prostaglandin E1 (PGE1) stimulated canine thyroid tissue in vitro, as exemplified by a 2- to 4-fold increase in glucose oxidation and a 40- to 100-fold increase in the number of intracellular colloid droplets. The effect on colloid droplets was detectable with a concentration of PGE1 as low as 10−7m and that on glucose oxidation at 10−6m. Both actions of PGE1 were inhibited by the lysosome stabilizer, chlorpromazine, and were additive with submaximal doses of TSH. The similarity of PGE1 action to that of TSH was also manifest in vivo; PGE1 stimulated both intracellular colloid droplet formation and 131I release. (Endocrinology86: 423, 1970)

Action mechanism of thyroid stimulating hormones (TSH and LATS)

TSH stimulates the secretion and synthesis of thyroid hormone, and also stimulates many metabolic pathways i.e, salt and water, carbohydrate, phosphorus and phospholipid, nucleic acid, amino acid and protein metabolism. Evidence has been accumulated that LATS causes a prolong effect on the thyroid and LATS differs in several respects from TSH. Until now the precise role of TSH and LATS at cellular level has not been known and the mode of action of two substances is not clear.In this paper, the metabolic effects of TSH and LATS on the thyroid were examined extensively using both in vitro and in vivo systems. The incorporation of 32P into the thyroid gland after a single injection of LATS and TSH was increased about 2 fold in the thyroxine treated mice. Also specific activities of RNA and phospholipid in the gland were increased remarkably. Experiments using 3H-uridine, TSH and LATS increased the incorporated radioactivity per RNA.A single injection of TSH or LATS into mice falied to stimulate the incorporation of 3H-leucine into thyroidal protein. While the continuous injection of LATS for 5 days caused increased thyroid weight, augmented protein content and increased incorporation of 3H-leucine. Also the specific activity of incorporated radioactivity per mg thyroid protein was significantly increased. Treatment with LATS or TSH for 8 days produced marked goiter formation accompanied by a high I131 thyroidal uptake. LATS stimulates protein synthesis in the gland, as does TSH.Using McKenzie's method, cyclic 3′5′ AMP (C 3′ 5′ AMP) and Dibutyryl cycilic 3′ 5′ AMP (D.C 3′ 5′ AMP) were found to increase thyroid hormone release from mouse thyroid in vivo. Other adenine nuclectides were also active. Simultaneous injection of theophylline and caffeine with C 3' 5' AMP and D.C 3′ 5′ AMP augmented the stimulatory effect of these adenine nucleotides on hormone release, although theophylline or caffeine had only a slight effect alone. No effect was obtained by the injection of NaF with D.C 3′ 5′ AMP. These adenine nucleotides have no enhancing action on hormone release from mouse thyroids during in vitro incubations, and no stimulatory effects were obtained by the nucleotides on the hydrolysis of thyroglobulin in mouse thyroid homogenates. These adenine nucleotides appeared to have no direct action on the enzyme participating in the breakdown of thyroglobulin.According to Pastan's method, the effect of TSH on cyclase activity was determined using beef and rabbit thyroid homogenate, but the increase of cyclic AMP synthesis from 3H-ATP (or 14C-ATP) was not obtained by the large doses of TSH. Similarly also LATS haven't any stimulating action on adenyl cyclase activity. NaF did not elevate adenyl cyclase activity, but inhibited ATP destruction by the inhibition of ATPase. Theophylline inhibited cyclic AMP destruction significantly. Using beef thyroid slices, 3H-adenine was preincubated for 1 hr and then TSH (Armour or NIH) or LATS was incubated for 30 min. with theophylline or NaF. The incorporated radioactivity into cyclic AMP in whole thyroid slice was examined. TSH and LATS similarly stimulated the incorporation of 131H-adenine into cyclic AMP in beef thyroid slice, especially in the presence of theophylline. However, the stimulatory effect of NaF on cyclic AMP formation was very slight.Both TSH and LATS elevated cyclic AMP levels in the gland, however it may be some of effects of both these thyroid stimulator. It is possible that TSH and LATS have similar stimulating action on various metabolism in the thyroid.

Effect of thyrotopin and the iodine content of the thyroid on the triiodothyronine: thyroxine ration of newly synthesized iodothyronines.

Massive doses of TSH (up to 13.5 U twice daily) given to rats fed a high iodine diet only slightly increased the 131I-labeled T3/T4 ratio (T3*/T4*)2 of newly iodinated thyroglobulin. Moderate doses of TSH (2 U daily) restored a proportionately higher rate of T3* than of T4* synthesis when administered to chronically hypophysectomized, iodine-depleted rats (T3*/T4*>1). Large doses of TSH (10 U daily) given to chronically hypophysectomized rats with a high thyroid iodine content only slightly inincreased T3*/T4* to 0.3 (us. 0.2 in intact controls). Doses of TSH which produced a high T3*/T4* in iodine-depleted, hypophysectomized rats did not do so in rats fed an iodine-deficient diet for 5 days to deplete the extrathyroidal iodide pool while maintaining a relatively high intrathyroidal iodine content. Pretreatment of these rats with 5 mg of perchlorate 30 min before radiodine administration to further reduce the quantity of iodide entering the thyroid did not increase the effectiveness of TSH on T3*/T4*. It ...

An in vitro bioassay for thyrotrophin (TSH).

The depression of 131I concentrating activity in propylthiouracil (PTU) blocked guinea pig thyroid slices has been utilized for the assay of TSH. The control iodide space was determined for each slice after 16 hr equilibration; TSH doses were then added and allowed to act for 10 hr. The effect metameter (the ratio of final to control T/M) eliminates variation due to non-uniformity of the mass of functional tissue assigned to each tube. High sensitivity and initial uptakes of 50–75% required for maximal precision are achieved by using thyroid tissue from guinea pigs treated chronically with PTU and withdrawn from goitrogen 72 hr before assay. The dose range for optimal precision extends from 1 to 64 μU International Standard TSH and from 2 to 16 μU human Research Standard A TSH (final concentration/ml in incubation medium). The limit of detection for TSH in unknown samples is about 0.5 mU/100 ml. Forty animals were tested in the assay to determine the homogeneity of the animal population with respect to se...

Early effects of thyrotropin on biosynthesis of thyroglobulin in the rat.

SummaryThe effect of a single dose of TSH on the incorporation in vivo of 14C labeled amino acids into thyroid proteins of the rat have been studied. Soluble thyroid proteins were analyzed by sucrose density-gradient ultracentrifugation. TSH, injected 2 to 4 hours before pulse-labeling, increased the total amount of 14C in protein and accelerated the appearance of label in 19 S thyroglobulin. When TSH was given within one hour of labeling or two hours afterwards, total 14C incorporation was unaffected, but the label appeared in mature (18-19 S) thyroglobulin at the expense of label in an immature (15-16 S) precursor protein. The results suggest that TSH produces an early stimulation of several phases of thyroglobulin biosynthesis.

Further Observations Concerning the EflFect of Actinomycin D on Thyroidal Iodide Transport in Rats

Previous findings from this laboratory concerning the ability of actinomycin D (act D) to enhance the thyroid/serum radioiodide concentration ratio (T/S) (3) were confirmed. This effect was not due to altered food intake, since it could be elicited in fasted animals. Act D did not interfere with the blocking influence of propylthiouracil on organic binding of 131I in the thyroid. A raised thyroid/medium radioiodide concentration ratio (T/M) could be observed when glands from intact rats injected with act D were incubated in a medium containing methimazole and 131I. The elevating influence of TSH injected into hypophysectomizedrats on the T/M established by their thyroids was not affected by act D given concurrently with the TSH. In contrast to the previous study (3), we found that act D consistently raised the T/S of untreated hypophysectomized rats. When it was given before the injection of a single dose of TSH into such animals, it did not prevent the initial drop in T/S. At or near the height of the T/...

Hypothyroidism induced by a transplanted fibrosarcoma in the rat.

ABSTRACT Rats bearing a methylcholanthrene induced fibrosarcoma showed a decrease in thyroid weight, a decreased responsiveness to the goitrogenous effect of PTU and a significant decrease in 24 hour thyroidal 131I uptake. The thyroid of the tumourous rats was also shown to have a marked inability to synthesize thyroid hormones. The effects on the thyroid were found to accumulate proportionally to the time during which the tumour grew in the rat, and lead to a fibrous and degenerative invasion of the thyroid gland. In the rats bearing tumours, 1) the plasma and the pituitary TSH concentrations were within normal range; 2) large doses of exogenous TSH were able to stimulate the thyroid; 3) injection of saline extracts from the tumour elicited thyroid changes similar to those produced by the tumour. It is concluded from these data that the tumour produces an unusual hypothyroidism in the rat, which is caused by a substance elaborated by the tumour. The substance destroys progressively the thyroid tissue, leaving less and less thyroid parenchyma to respond to TSH and to secrete thyroid hormones. The substance seems to interfere with TSH at the thyroid level.

THE RESPONSE OF THE THYROID GLAND TO THYROID-STIMULATING HORMONE (TSH) IN INFANTS WITH MALNUTRITION

The thyroid response to TSH was studied in a group of 16 infants with severe marasmus and 9 normal controls of the same age. The radioiodine uptake, the BEI, and the oxygen consumption were determined in both groups before and after the administration of a single dose of TSH. The results suggest that the low function of thyroid gland found in marasmic infants is due mainly to a decrease of TSH stimulation but there is also a deficit of thyroid function per se. These results are discussed in relation to previous data.

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...

A re-examination of the goldfish microhistometric assay method for thyrotropin

1. The performance of the goldfish microhistometric assay method with bovine TSH has been studied under defined experimental conditions. 2. A linear relation between the log of the total dose of bovine TSH and the mean thyroid cell height of the pharyngeal thyroid has been found. 3. The sensitivity of this assay, under the experimental conditions, is, at least, 0.024 IU of TSH and the index of precision of the method is 0.362. 4. The possible influence of sex, duration of injection, photoperiod, temperature, nature of diet, and fasting on the characteristics of this assay are discussed.

Effect of excess iodide on thyroid hormone synthesis in hypophysectomized, thyrotropin administered rats

Since the inhibitory effect of excess iodide on thyroid hormone formation continues only for 24 hours or so in experimental animals as well as in man, it is not possible to obtain a clue as to what happens later during the course of iodide therapy in Graves' disease or why relapse occurs while full doses of iodide are being given. In an attempt to explore these problems, hypophysectomized animals were made hyperthyroid by administering large doses of TSH for 10 days, and effect of excess iodide on thyroid weight and thyroid hormone synthesis was studied. In normal animals, thyroid hormone synthesis was inhibited only for 24 hours or so even though the administration of excess iodide was continued for a prolonged period. Thyroid weight was not affected by excess iodide regardless of the duration of iodide treatment in normal animals. In contrast, in hypophysectomized, TSH-treated animals, thyroid hormone concentration in the thyroid decreased significantly and iodide concentration contrary increased after the administration of excess iodide for 3 days. A marked shrinkage of thyroid size was also produced by the administration of excess iodide for 3 days. However, hypertrophied adrenals and testis produced by the contaminants of TSH were not affected by excess iodide. Since observed effects of excess iodide could not be explained on the basis that disappearance rate of TSH is faster in animals treated with both TSH and iodide, it is concluded that excess iodide exerts its inhibitory effect on the thyroid for 3 days in hyperthyroid animals. Although the period of iodide treatment was restricted by the large quantities of TSH involved, our data offer a route for future experimental attempts to produce the continuous inhibition of thyroid hormone synthesis by excess iodide in the rat.

EFFECT OF SPECIES DIFFERENCES OF MICE ON THE BIO-ASSAY OF THYROTROPIN.

The McKenzie bio-assay for TSH was modified to permit the handling of large numbers of mice and the consequent analysis of many samples during a single assay run. An attempt was made to find a strain of mice significantly more sensitive to TSH than the Swiss-Webster albino (SWA) animals normally used. Twenty-two strains of inbred mice and 2 strains of deer mice (Peromyscus maniculalus) were tested. The results of the assays of the various strains of animals were computed with the aid of a digital computer. The relation between the logarithm of the responses to TSH and the doses of TSH was found to be the most useful index. The deer mice were insensitive to the doses of TSH used. Although some of the strains of inbred mice were found to be significantly more sensitive to TSH than the SWA controls, in no case was the increased sensitivity of the inbred mice sufficient to increase the usefulness of the assay. (Endocrinology 76: 890, 1965)

EFFECT OF INJECTED THYROTROPIC HORMONE ON THE IN VITRO UPTAKE AND METABOLISM OF 131-I BY THYROID GLANDS OF FETAL AND NEWBORN RATS.

Intact thyroid gland lobes of fetal, newborn and adult rats, and slices prepared from glands of adult rats, all of which had been injected with identical doses of TSH in relation to body weight, were incubated in a Ringer-bicarbonate medium containing 131I, and their incorporation of the labeled iodine into iodoamino acids was compared. A distinct difference between the 131I metabolism of the intact lobe and slices of the adult rat thyroid gland was observed. This consisted of a greater uptake of the added 131I and its incorporation into DIT by the lobes. The finding that early after a TSH injection the 131I uptake by the incubated intact thyroid lobe of adult rat is diminished is confirmed. This was not observed in the experiments with slices. Under identical hormone treatments, the incubated thyroid glands of fetuses and newborn rats were much more responsive to injected TSH than were those of adult rats. A dual action of TSH on 131I metabolism by the incubated thyroid lobe of fetuses and newborn rats w...

STUDIES ON THE STIMULATION OF THYROIDAL INORGANIC 127-IODIDE RELEASE IN VITRO BY THYROTROPIN.

When beef thyroid slices were incubated with thyrotropin (TSH), inorganic 127iodide accumulated in a rectilinear fashion for up to 8 hr of incubation, whereas little change was noted in controls. An oxygen atmosphere was essential for this effect. The log-dose response curve was biphasic, with hormone concentrations ranging from 0.01 to 100 mU/ml incubation medium. Maximum increases in stable iodide were achieved at 1 mU/ml TSH levels. Thiourea and/or perchlorate did not alter this biphasic response. TSH inhibited the protein binding of added radioiodide after 5 hr of incubation, although slice uptake was not impaired. Again the dose response was biphasic, with 1 mU/ml concentrations appearing to be most effective. In shorter incubations, however, the larger TSH doses increased radioiodine organification. Deiodination per se, as measured by the accumulation of radioiodide from diiodotyrosine- 131I in the presence of an excess of added carrier diiodotyrosine, was not stimulated by TSH. These data indicate ...

THE EFFECT OF THYROTROPHIC HORMONE ON THE POTASSIUM CONTENT OF MUSCLE AND LIVER TISSUE AND ON THE BLOOD SUGAR LEVEL IN GUINEA PIGS.

ABSTRACT The investigation showed that a single subcutaneous injection of thyrotrophic hormone (TSH) in young guinea pigs does not produce any change in the potassium content of striated muscle or of the liver within 2 hours of the injection, but does induce hyperglycaemia within this period. In a previous investigation (Gedda 1960), it was demonstrated that an equally large dose of TSH produced a marked increase in the potassium content of the thyroid gland of the guinea pig within 2 hours. The observations made in the present investigation support the assumption that the increase in potassium in the thyroid gland is specific to the gland after stimulation with TSH and that the increase is not secondary to a primary hypoglycaemia.

Effect of relaxin on thyroid function in the rat.

SUMMARY 1. Relaxin administered to intact female rats at oestrus stimulated an increase in 24 hr. uptake of 131I by the thyroid gland. 2. In oestrogen-treated spayed rats, relaxin stimulated increases in 24 hr. thyroidal uptake of 131I, thyroid weight and plasma PB131I to levels which were significantly higher than in the oestrogen treated controls. 3. The effect of relaxin on the thyroid was not observed in oestrogen-treated hypophysectomized female rats or in hypophysectomized rats on a maintenance dose of TSH. 4. It is concluded that relaxin causes an increase in size of the thyroid and uptake of radioactive iodine (RAI) in oestrogen-primed animals by means of an increased production of TSH. Two mechanisms by which TSH production may be stimulated under these experimental conditions are discussed.

EFFECT OF NOR-ADRENALINE ON THE RESPONSE OF THE THYROID TO THYROTROPHIC HORMONE

ABSTRACT It has been shown that the combination of thyrotrophin and nor-adrenaline – each in a dose which is ineffective when given alone – increases the amount of the PB131I in the plasma of the thyroid vein. The enhancing effect of nor-adrenaline was clearly observed when the thyroid-stimulating dose of TSH was fixed at a suboptimal level, which did not make the thyroid respond to the full limits of its functional capacity. Under the experimental conditions described, it appears reasonable to assume a functional synergism between TSH and nor-adrenaline.

Sensitivity to thyrotropin in two subspecies of deermice ( Peromyscus maniculatus) and albino-Swiss mouse as measured by I 131 depletion

The sensitivity of the thyroid gland to thyrotropin was determined in two subspecies of deermice and in the albino-Swiss mouse by means of the thyroidal I 131 depletion test. A 45% I 131 depletion was obtained at 12 hr in P. m. bairdii after treatment with 0.01 U.S.P. units of TSH as compared to 27% and 8% depletion in P. m. gracilis and the albino-Swiss mouse, respectively. At doses of TSH ranging from 0.01 to 0.5 U.S.P. units, bairdii demonstrated a consistently greater depletion of thyroidal I 131 than gracilis or the albino-Swiss mouse. Generally, it was found that the thyroid gland of bairdii indicated a significantly higher level of sensitivity to exogenous thyrotropin levels.

The effect of purified bovine thyroid-stimulating hormone in men. II. Loss of effectiveness with prolonged administration.

Four normal human subjects received repeated doses of a highly purified bovine thyrotropin (prepared by the method of Pierce et al.) and the response was monitored by the rise in the two-hour thyroidal uptake of I132. All subjects initially responded to doses of TSH varying from 0.0032 to 0.050 unit per Kg. of body weight. All became refractory to the effects of the TSH after five to twenty-nine doses. Sera obtained after development of resistance contained hemagglutinating and neutralizing antibodies to thyrotropin.

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 ...