Administration Of Thyrotropin Research Articles

The effect of marihuana on pituitary-thyroid activity in the rat.

Systemic injection of marihuana distillate extract, of whichΔ9-tetrahydrocannbinol (Δ9-THC) is the major single constituent, inhibits the release of radioiodine from the thyroid gland of the rat. Administration of thyroid stimulating hormone (TSH) resulted in increased output of iodine in animals pretreated withΔ9-THC. These data suggest that reduced TSH secretion is the primary cause of the thyroid inhibition induced by THC. Bilateral electrolytic lesions in the region of the medial mammillary nuclei of the hypothalamus prevented the decrease in pituitary-thyroid activity induced by THC, whereas lesions in the rostral hypothalamus did not effect the response. These results indicate that THC inhibits pituitary-thyroid function due to an action on neurons in the caudal hypothalamus. The possibility is discussed that these effects are due to stimulation of specific inhibitory centers rather than depression of neurons responsible for tonic release of TSH. Marihuana appears to have a similar action to morphine in modifying pituitary-thyroid function.

Stimulation of proteolysis in the mouse thyroid gland by thyrotropin and the long-acting thyroid stimulator: comparison of intact lobe and homogenate.

Thyrotropin given in vivo stimulated in vitro proteolysis of 125I-labeled thyroglobulin in the thyroid of mice; with intact lobes optimal pH was 7.4 and in homogenates proteolysis was maximal at pH 5.0. The stimulation of proteolysis in intact lobes was otherwise similar to that observed using homogenates. The lowest dose of thyrotropin that gave a significant response was 1 mU in normal mice and 0.1 mU in mice treated with thyroid hormone. LATS given in vivo significantly increased the in vitro proteolysis of endogenous thyroglobulin. There was enrichment of both radioactivity and proteolytic activity in the 15,000 ×g pellet of thyroid homogenate after in vivo administration of thyrotropin, but not if there was an intervening period of incubation of intact lobes before homogenization. Actinomycin D pretreatment,known to inhibit the release of radioiodine from the mouse thyroid in vivo, partly reduced the thyrotropin-induced stimulation of proteolysis at pH 7.4 as well as at pH 5.0. When rat thyroglobulin...

OPHTHALMIC GRAVES' DISEASE: Diagnosis and Pathogenesis

Ophthalmic Graves' disease is the term used to describe the ocular manifestations of Graves' disease in patients who are euthyroid and have no past history suggesting hyperthyroidism. The clinical and laboratory features of 26 such patients are presented. The eye signs are commonly asymmetrical. Goitres, often small, were present in 9 patients, vitiligo in 2, and a family history of thyroid disease or pernicious anæmia in 7. The six-hour-radioiodine uptake was not suppressed by triiodothyronine in half the patients, only 1 of whom subsequently developed hyperthyroidism. 5 out of 9 patients showed a rise in radioiodine uptake after administration of thyroid-stimulating hormone, and in 8 of these the serum-protein-bound iodine was raised. 5 out of 6 patients showed a greater-than-normal suppression of radioiodine uptake by iodides. The incidence of thyroid and gastric antibodies was significantly higher than in matched controls, and a third of all the patients had high titres of thyroid antibodies similar to those in patients with Hashimoto's disease. The incidence of high titres of thyroglobulin antibodies was significantly higher than in patients with Graves' disease who were hyperthyroid. The long-acting thyroid stimulator (L.A.T.S.) could only be detected in the serum of 2 patients. These results indicate the presence of some thyroid abnormality in the majority of patients with ophthalmic Graves' disease but suggest that L.A.T.S. is unlikely to be a major factor in the pathogenesis.

Effects of thyrotropin on 35S-sulfate uptake by mouse Harderian gland.

A single ip injection of 10 mU thyrotropin stimulated the 6 hr uptake by the mouse harderian gland of simultaneously administered 35S-radiosulfate; higher doses of thyrotropin did not enhance the response. Increased 38S incorporation into sulfated glycosaminoglycans, especially keratan sulfate and dermatan sulfate, occurred after administration of thyrotropin. The thyrotropin effect was not organ specific as other tissues (salivary gland, pancreas) also showed increased 35S uptake. The responseresponse of the harderian gland to rat pituitary homogenate was similar to that to an equipotent dose of relatively purified NIH-TSH. The 36S uptake by various tissues of hypophysectomized mice was almost twice that observed in intact animals and was further increased by administration of thyrotropin. Human sera containing the long-acting thyroid stimulator in high titer had no effect on the harderian gland uptake of radiosulfate. (Endocrinology 85: 952, 1969)

Endemic goiter in the Cauca Valley. II. Studies of thyroid pathophysiology.

ABSTRACT Prolonged supplementation with adequate or even high amounts of dietary iodine of 317 goitrous and 200 nongoitrous individuals from the endemic area of the Cauca Valley resulted in thyroidal 131I uptakes within the low normal range of values reported from nonendemic areas; serum PBI concentrations were similar to those accepted as normal; and urinary iodine excretions were above the levels observed in non-endemic areas. Normal renal clearances of iodine and high plasma inorganic iodide (PII) have also been found. The increments in thyroidal 131I uptakes and PB127I concentrations after the administration of thyrotropin, normal values for PB131I and normal conversion ratios indicate that goitrous glands from the Cauca Valley are normally sensitive to tropic hormone, are not under maximal endogenous TSH stimulation, and therefore have an adequate functional reserve. Thus, it appears that intrathyroidal factors and not TSH activity account for the retardation in hormonal synthesis that has been encou...

Early Changes in the Fine Structure of the Thyroid of Midlethally Irradiated Dogs

Changes in the fine structure of the thyroid follicular epithelium at selected times during the first week after midlethal irradiation of young dogs were similar to those seen after the administration of thyroid stimulating hormone. This similarity supports the observations of others that the early thyroid response is mediated by increased pituitary activity. The hypertrophy and edema of the endothelial cells of small blood vessels soon after irradiation and the subsequent endothelial atrophy seen later were consistent with the hemorrhagic diathesis which undoubtedly would have developed in these dogs.

The Thyrotrophin Stimulation Test

Three-day and single-dose thyroid-stimulating hormone (TSH) tests were performed in 211 subjects with suspected or known thyroid hypofunction. Both procedures differentiated between euthyroidism and hypothyroidism. The mean changes in 24-hr 131I uptake after 3-day dosage with TSH and in 3-hr 131I uptake after one dose of TSH were significantly greater in euthyroid than in hypothyroid subjects. Comparable separation was afforded by concomitant measurement of plasma protein-bound iodine (PBI) before and after TSH administration with either the three-dose or single-dose procedure. Use of 10 units rather than 5 units TSH in the single-dose procedure did not increase its diagnostic sensitivity. The single-dose TSH test was valuable in characterizing euthyroidism in subjects receiving thyroid hormone because of an unconfirmed and erroneous prior diagnosis of hypothyroidism. Laboratory diagnosis of "low thyroid reserve" does not preclude subsequent long-standing euthyroidism as demonstrated in 10 to 12 patients so diagnosed and followed for 2 to 6 years. TSH testing of euthyroid subjects with multi-nodular goiter showed relatively impaired 131I uptake response, although normal post-TSH PBI increase was observed. Although the 3-day TSH test distinguished hypopituitary patients from those with primary hypothyroidism, neither 5-unit nor 10-unit single-dose TSH tests permitted differentiation between these two patient groups.

Inhibition of organic binding of iodine with graded doses of iodine in euthyroid men.

ABSTRACT The inhibition of thyroidal organic binding of iodine by iodide (Wolff-Chaikoff effect) was studied in 15 euthyroid men. The subjects received 5 U thyrotropin im for 3 consecutive days and varying doses of iodide for 48 hr before measuring the thyroid uptake of 132I. After the determination of the 3 hr thyroid 132I uptake, serum iodide, and thyroid iodide uptake, 1 g potassium perchlorate was given orally and thyroid 132I was measured 1 hr later. A positive response indicative of inhibition of organic binding was defined as a loss of 15% 132I in the thyroid at 3 hr. The base line thyroid uptake (5.00 ± 0.96%) and thyroid iodide uptake (4.48 ± 0.53 μg/hr) increased 3-fold with the administration of thyrotropin. As iodide intake increased, the serum iodide increased, the thyroid 132I uptake fell, but the thyroid iodide uptake increased progressively. A positive perchlorate response occurred in 11 subjects at iodide doses ranging from 1 to 16 mg daily, serum iodide concentrations of 2.5 to 36.9 μg/1...

Thyroidal content of thyrocalcitonin in hypothyroid and hyperthyroid rats.

The thyrocalcitonin content of the thyroid glands of euthyroid, hyperthyroid and hypothyroid rats fed a calcium deficient diet was determined in 2 separate experiments by bioassay. Hyperthyroidism was produced by the injection of 50 μg l-thyroxine or 200 mU thyrotropin per day, and hypothyroidism by the dietary administration of 0.05% propylthiouracil or an iodine deficient diet. The log-dose response curve for the hypocalcemic activity of the thyroid homogenates from the euthyroid rats was linear between 0.24 and 0.96 mg thyroid tissue, equivalent to 0.018–0.072 of a single rat thyroid gland. No significant differences in the hypocalcemic response of assay rats was observed when a comparison was made of thyroid tissue homogenates that included parathyroid tissue and thyroid homogenates in which the parathyroid gland was removed prior to tissue homogenization. Thyroxine consistently caused a significant 27–35% reduction in the thyroidal content of thyrocalcitonin, whereas the administration of thyrotropin...

The lymphatic and venous pathways for the outflow of thyroxine, iodoprotein and inorganic iodide from the thyroid gland.

1. Baboons and cats were given radioactive iodine and, at varying times after the injection, samples of thyroid and non-thyroid lymph and of thyroid venous and peripheral venous blood were collected. The radioactive material in these samples was separated by paper chromatography or by differential precipitation and solvent extraction into three main fractions: inorganic iodide, iodoamino acid iodine and high molecular-weight material (retained at the origin of chromatograms and not extractable by butanol or ethanol). The latter was considered to be iodoprotein.2. Thyroxine was the main component of the radioactive iodoamino acid iodine in thyroid lymph, in thyroid venous and in peripheral blood. The concentration of thyroxine radioactivity in the thyroid lymph was several times greater than that in either thyroid venous or peripheral blood plasma, both before and after giving thyroid stimulating hormone.3. An unidentified thyronine compound that was frequently found in thyroid lymph and also in blood samples contained an appreciable proportion of the radioactive iodine. This substance was probably a metabolite of one of the iodothyronines. In addition, iodotyrosines probably accounted for up to 4% of the radioactivity in the lymph and blood samples but radioactive triiodothyronine could not be detected with certainty.4. In some experiments lymph was obtained from the cervical lymph trunk at a considerable distance from the thyroid gland, in order to avoid operative trauma to the gland. This cervical lymph contained diluted thyroid lymph but even so it contained more radioactivity in the form of iodoamino acid and iodoprotein than did peripheral blood or non-thyroid lymph. Cervical lymph and thyroid lymph both contained less radioactive inorganic iodide than did non-thyroid lymph.5. The administration of thyroid stimulating hormone caused a prolonged rise in the output of radioactive iodoamino acid in the thyroid venous blood and, for a limited period, an increase in the output of radioactive inorganic iodide. At the same time there was an increase in the output of radioactive material in the thyroid lymph. The main part of the latter was due to a rise in the output of iodoprotein.6. The lymphatics and the venous system provide alternative pathways for the outflow of iodine compounds from the thyroid gland. These pathways differ in relative importance for different iodine compounds. For iodoprotein the lymphatic pathway is the important one since there is no appreciable release of this substance into the thyroid venous blood. In the case of inorganic iodide, where there is no appreciable difference in concentration between thyroid lymph and blood, the greater flow of blood makes the venous pathway relatively more important than the lymphatic one. Thyroxine is released into the thyroid lymph in higher concentration than into the blood but the faster flow of blood makes the venous pathway relatively more important.

Effect of stimulation and suppression of the thyroid gland upon production of iodoprotein in man

Iodinated components of serum were studied in 6 normal subjects and 10 patients with nontoxic goiter. After administration of I 125, serum specimens were analyzed by column chromatography using anion exchange resin (Dowex 1 × 2) and radioactivity was measured in 4 fractions: iodoprotein, iodotyrosine, iodothyronine and iodide. After 2 weeks, about 25 per cent of the radioactivity was found in the iodoprotein fraction of serum of normal subjects and 44 per cent in that of goitrous patients. Butanol-insoluble iodine (BII) was determined in 36 normal subjects and 26 patients with nontoxic goiter; the mean BII was 26 per cent of the total protein-bound iodine in the normal group, and 45 per cent in that of the goitrous group. The authors suggest that butanol-insoluble iodoprotein is present in serum of normal subjects but is in much larger amounts in that of goitrous patients. Production of iodoprotein could be suppressed by administration of thyroxin. Administration of thyroid-stimulating hormone (TSH) to normal subjects doubled production of iodoprotein and iodothyronine, but caused a more irregular response in patients with goiter. Gel filtration through Sephadex G-100 and salting-out in potassium phosphate showed that iodoprotein from goitrous subjects resembles iodoalbumin. Iodoprotein synthesis is a major pathway of iodine metabolism in patients with nontoxic goiter. This pathway is regulated by thyrotropin as it can be suppressed by thyroxin and activated by TSH.

Changes in fine structure and acid phosphatase localization in rat thyroid cells following thyrotropin administration.

Shortly after the administration of 1/40 unit thyrotropin to rats, 24 hours post-hypophysectomy, the following sequence of changes has been observed within thyroid follicular epithelial cells: (1) the appearance of apical cell surface activity consisting of pseudopods projecting into the follicular lumen; (2) apparent phagocytic engulfment of colloid droplets lacking indications of acid phosphatase activity; (3) close association and probable fusion of newly formed colloid droplets and dense granules, the latter cytochemically positive for acid phosphatase activity; (4) the appearance of presumptive acid phosphatase activity within colloid droplets; and, (5) further colloid droplet changes, viz., basipetal migration and decrease in size, accompanied by an increase in density and in demonstrable acid phosphatase activity. These changes appeared to represent the resorption and degradation of follicular colloid. Comparable results were obtained using intact and more heavily stimulated animals. Colloid biosynthesis was tentatively visualized in these cells as a separate mechanism involving small vesicles prominent in the Golgi region and beneath the apical plasma membrane of some, but not all, thyroid follicular cells in each specimen.

LOCALIZATION OF ESTERASE AND ACID PHOSPHATASE IN GRANULES AND COLLOID DROPLETS IN RAT THYROID EPITHELIUM.

Droplets which stain like colloid occur in the cytoplasm of the thyroid follicular epithelium of the rat following stimulation of the gland by thyroid-stimulating hormone (TSH). The occurrence of droplets was remarkably reduced when the lumen became depleted of colloid. Acid phosphatase and esterase were localized in the thyroid droplets and, in addition, in granules largely around the nucleus. Stimulation by TSH resulted in an increase in the number of droplets containing enzyme. Twenty-four hours after hypophysectomy, enzyme-associated granules were localized at the basal end of the cell and droplets were absent. Intravenous injection of TSH resulted in formation of droplets at the apical end of the cell and migration of enzyme-associated granules toward the apical end of the cell. The droplets were first observed approximately 10 minutes after TSH administration and at this time did not appear to contain enzyme. Within 15 minutes many droplets contained enzyme. The granules were largely localized near the nucleus on its apical side 30 minutes after a dose of 25 milliunits of TSH, but were less well localized following one-tenth this dose. These results indicate that the epithelial cell of the thyroid gland contains preformed hydrolytic enzymes associated with granules (lysosomes). When the gland is stimulated by TSH, droplets are formed from colloid derived from the lumen (phagosomes), and hydrolytic enzymes are transferred from granules to the droplets. The droplets may be intracellular organelles for hydrolysis of colloid and liberation of thyroxine prior to the release of thyroxine into the blood.

THE EFFECT OF ANTERIOR PITUITARY HORMONES ON EXPERIMENTALLY INDUCED MUSCULAR ATROPHY AND ON TIBIAL EPIPHYSIAL CARTILAGE WIDTH IN NORMAL AND HYPOPHYSECTOMIZED RATS.

SUMMARY 1. Unilateral section of the sciatic nerve causes atrophy of the gastrocnemius muscle with consequent reduction in wet weight and in fibre size of the muscle in both hypophysectomized and non-hypophysectomized animals. 2. The administration of growth hormone, thyroid-stimulating hormone (TSH), follicle-stimulating, luteinizing and adrenocorticotrophic hormone, either before nerve section, immediately after nerve section or some time after atrophy has been established, had no effect on muscle fibre size. 3. The administration of TSH during the period immediately following nerve section caused a significant reduction in the tibial epiphysial cartilage width of the denervated limb. No difference in cartilage width between denervated and innervated limbs was observed following treatment with any of the other hormones. 4. In both normal and hypophysectomized animals the effect of the hormones on body weight and on the weight of normal and atrophic muscles was in keeping with their known physiological actions. 5. It is concluded that anterior pituitary hormones act on muscles by virtue of their well-known anabolic or catabolic properties, that their effects on total body weight and innervated and denervated muscle are generally similar and that, under the experimental conditions used, none of the hormones studied was capable of preventing the occurrence of atrophy in denervated muscle.

DEPLETION OF THYROID GLANDULAR IODINE AFTER ADMINISTRATION OF THYROTROPIN.

Thyroid content of iodine and of iodoamino acids released by enzymic proteolysis of thyroid tissue was measured before and 3 hr after the intravenous administration of thyrotropin to rats whose glands had been labeled with I131. The thyrotropin-induced loss of radioiodine was considerably greater when animals were given propylthiouracil shortly before injection of thyrotropin than when given saline. In propylthiouraciltreated animals the iodotyrosines and iodothyronines disappeared from the gland in the proportions in which they were present in the gland, while, in animals not given propylthiouracil, thyrotropin induced a relatively greater depletion of iodotyrosines than of iodothyronines. Specific activity data suggested that conversion of iodotyrosines to iodothyronines was accelerated during the 3-hr interval after injecting thyrotropin in control animals while this was probably prevented in the animals given propylthiouracil. Inhibition by propylthiouracil of the conversion of iodotyrosine to iodothy...

CHANGES IN THYROIDAL FUNCTION DURING ADAPTATION TO LARGE DOSES OF IODIDE.

Studies were conducted to determine the mechanism whereby the acute inhibitory effect of large doses of iodide on the organic binding of thyroidal iodide (Wolff-Chaikoff effect) is overcome during prolonged iodide administration (adaptation or escape phenomenon). Thyroids of control rats and of rats adapted to iodide in vivo were freed of inorganic iodide by in vivo administration of thiocyanate and in vitro leaching, and were then incubated in media containing inorganic I/sup 131/ of widely varying specific activity. In vitro, when exposed to low concentrations of extracellular iodide, thyroids of control animals accumulated and organically bound more iodine than did adapted glands. As the extracellular iodide concentration was increased, the total iodine accumulation in control thyroids increased; however, the quantity of iodine bound organically ultimately declined. At this point, ratios of labeled mono- to diiodotyrosine rose. Thus, a Wolff-Chaikoff effect was induced in vitro in control glands. In adapted thyroids, far less iodine entered the thyroid, but especially at higher concentrations of extracellular iodide, the percentage of accumulated iodide bound organically did not decline so rapidly as in controls. As a result, total organic binding rose progressively and, at high iodide concentrations in the medium, exceeded that in control glands.more » Mono- to diiodotyrosine ratios did not increase. Thus, escape from the inhlbitory effects of iodide was evident in vitro in adapted thyroids. At each concentration of extracellular iodide, far less inorganic iodide was found in adapted than in control glands, and the concentration of thyroidal iodide achieved by adapted thyroids at the highest medium iodide concentratl ons used was far less than that sufficient to induce the Wolff-Chaikoff effect in control glands. In the presence of blocking concentrations of methimazole, the iodidetransport capacity of adapted thyroids was far lower than that of control glands. Qualitatively similar data were obtained in studies of the thyroids of control and adapted hypophysectomized rats. Administration of thyroid-stimulating hormone to adapted rats did not alter their in vitro iodine metabolism, or their ability to resist the inhibitory effects of high concentrations of extracellular iodide. These data suggest that adaptation to the inhibitory effects of large doses of iodide occurs through an intrinsic thyroidal mechanism that reduces the thyroidal iodidetransport capacity and thereby allows intrathyroidal iodide to decline to concentrations insufficient to sustain the Wolff-Chaikoff effect. (auth)« less

Effect of injection of thyrotropin upon deiodination of diiodotyrosine by rat thyroid and liver.

Intravenous administration of thyrotropin in rats resulted in prompt enhancement of the deiodinating activity of thyroid tissue, as judged by the formation of labeled iodide in gland homogenates incubated with labeled diiodotyrosine. Deiodinating activity of thyroid tissue was significantly greater than in the controls within 3 hr after TSH injection, and the increased activity persisted for at least 24 hr. The deiodinating activity of liver slices and homogenates was not modified by the administration of TSH. Deiodinating activity of thyroid homogenates was greatly enhanced by addition of TPNH to the incubation medium; in such fortified homogenates, the deiodinating activity of thyroid tissue of TSH-treated rats was not appreciably different from that of the controls. The results suggest that TSH-induced stimulation of thyroidal deiodinating activity may be related to an increased glandular concentration of TPNH.

Effect of thyroidstimulating hormone (TSH) on the accumulation of perchlorate and fluoroborate ions in the thyroid glands of rats.

The effect of Thyroid Stimulating Hormone (TSH) on the concentration of perchlorate and fluoroborate ions in the thyroid glands of rats was investigated. The results show an increase in the concentration ratio of these ions in mg of thyroid—over concentration in mg of serum (T/S), 24 hours after administration of TSH. The nonspecific nature of the regulatory mechanism in the trapping stage of the thyroid gland is demonstrated.

Thyroid function and periodic paralysis

The effects of 1-triiodothyronine and thyrotropin were investigated in a case of familial periodic paralysis. Hypermetabolism, first induced by the administration of 1-triiodothyronine then by thyrotropin, had no immediate adverse effects on the periodic paralysis. Exacerbations of the disease occurred twice, each time with return of the basal metabolic rate to normal. The increased weakness following withdrawal of l-triiodothyronine was promptly reversed by the administration of thyrotropin. The increased weakness following thyrotropin withdrawal disappeared gradually over twentyfive days. Thyroid hormones rather than pituitary thyrotropin secretion determined the effects on the periodic paralysis. Exacerbations of the disease were not associated with depression of the serum potassium levels. Decreased urinary excretion of potassium was noted during the first exacerbation, and decreased excretion of potassium and sodium were noted preceding the second one. No support could be found for the assumption that the two exacerbations were caused by temporary hyperaldosteronism. The present study points to a difference in the basic abnormality between the thyrotoxic and the familial forms of periodic paralysis.

Electrocardiographic changes following the administration of thyroid stimulating hormone (thyrotropin) ∗

In three of five men, aged forty-six to ninety-two, the intramuscular administration of 25 mg. (10 U.S.P. units) of thyroid stimulating hormone (thyrotropin; TSH) on each of four or five successive days, produced electrocardiographic evidence of changes in myocardial irritability and repolarization which appeared and declined early in relation to change in heart rate and basal metabolic rate. The nature and time course of these changes may provide information on the mechanism of thyroid stimulation of the heart, and are compatible with an hypothesis that thyroidal effects on the heart are, at least in part, mediated by a sympathomimetic mechanism. Other explanations are not excluded. The observations are of clinical interest and may suggest a test of the above hypothesis in man.