Tadpole Metamorphosis Research Articles

Thyroid Disorders—A Half-century of Innovation.

s1 May 1965Thyroid Disorders—A Half-century of Innovation.E. B. Astwood, M.D., F.A.C.P.E. B. Astwood, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-62-5-1079_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWhat might be called the golden age of the thyroid was initiated 50 years ago when new developments flowed from all directions. Experiments on the prevention of simple goiter with iodine were made then, thyroxine was isolated from the thyroid gland, metamorphosis in tadpoles was shown to be mediated by the gland, and some hint of a controlling influence from the pituitary was beginning to be envisioned. Within 15 years the structure of thyroxine was elucidated, iodine had been reintroduced in the treatment of hyperthyroidism, and goiter from feeding cabbage had been described. When radioiodine and antithyroid drugs came into... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1965Volume 62, Issue 5Page: 1079-1079KeywordsDrugsHyperthyroidismThyroidThyroxine Issue Published: 1 May 1965 PDF downloadLoading ...

The effects of chemical derivatives of thyroid-stimulating hormone on the metamorphosis of Rana pipiens tadpoles

Thirty-nine different chemically modified derivatives of TSH preparations have been studied on metamorphosis of Rana pipiens tadpoles. The results indicate that derivatives prepared under a wide range of conditions show various degrees of metamorphosing ability when tested in the tadpole. None of the derivatives gave evidence of inhibiting simultaneously administered TSH, or preventing normal metamorphosis.

Synthesis in vitro of thyroxine from diiodotyrosine by myeloperoxidase and by a cell-free preparation of beef thyroid glands II. Flavin mononucleotide and Mn2+ system

1.1. Thyroxine was identified by paper chromatography as one of the products of the action of a purified peroxidase, myeloperoxidase, on diiodotyrosine in the presence of FMN, MnCl2 and light as a hydrogen peroxide-generating system.2.2. The incubation of diiodotyrosine with a cell-free thyroid particulate preparation under comparable conditions also led to the formation of thyroxine which was identified by paper chromatography, ultraviolet and infrared analyses and by the stimulation of tadpole metamorphosis.3.3. The synthesis of thyroxine was inhibited by ergothioneine, reduced gluthione, ascorbic acid, semicarbazide, Tapazole, 2-thiouracil and catalase (EC 1.11.1.6).4.4. Significant amounts of ammonia were released on the incubation of diiodotyrosine with either myeloperoxidase or the thyroid particulate fraction in the presence of FMN, MnCl2 and light. Ammonia release was inhibited by the same reagents that inhibited thyroxine synthesis.5.5. The synthesis of thyroxine in the flavin system differed from the synthesis in the glucose and glucose oxidase system1 in several respects: heat inactivation; specificity for the thyroid particulate fraction; effect of serotonin.6.6. These results are discussed in relation to the possible involvement of a non-specific protein “activation”, in addition to a thyroid peroxidase, in the synthesis of thyroxine from diiodotyrosine in the presence of FMN, MnCl2 and light.7.7. The possibility that there existed a peroxidase catalyzed transiodination of iodide from diiodotyrosine to endogenous free thyronines was entertained. Under the experimental conditions employed in this study, such a reaction is considered unlikely.

Synthesis in vitro of thyroxine from diiodotyrosine by myeloperoxidase and by a cell-free preparation of beef thyroid glands I. glucose-glucose oxidase system

1.1. The action of a purified peroxidase, myeloperoxidase, on diiodotyrosine was investigated in the presence of glucose and glucose oxidase as a hydrogen peroxide, generating system. Thyroxine was identified by paper chromatography as one of the reaction products.2.2. The incubation of diiodotyrosine with a cell-free thyroid particulate preparation under similar conditions also led to the formation of a substance which was indistinguishable from thyroxine by paper chromatography, ultraviolet and infrared analyses and by its stimulation of tadpole metamorphosis.3.3. The synthesis of thyroxine was inhibited by ergothioneine, reduced glutathione, ascorbic acid, semicarbazide, Tapazole, 2-thiouracil and catalase.4.4. Significant amounts of ammonia were released on the incubation of diiodotyrosine with either myeloperoxidase or the thyroid preparation in the presence of glucose and glucose oxidase.5.5. These results are discussed in relation to the mechanism of thyroxine synthesis by peroxidase. The involvement of a thyroid peroxidase in the synthesis of thyroxine from diiodotyrosine by the thyroid particulate preparation under the conditions employed in this study is suggested.

The effect of sodium fluoride on the metamorphosis of tadpoles.

The effect of sodium fluoride on the metamorphosis of tadpoles.

Thyroxine Vs. Triiodothyronine in the Fowl

Following the discovery of a previously unrecognized iodinated compound in mammalian thyroid and plasma (Gross et al. 1950), Gross and Pitt-Rivers (1952) identified the compound as 3:5:3′-l-triiodothyronine. Many subsequent investigations have shown that l-triiodothyronine (T-3) is several times as potent as l-thyroxine (T-4), as judged by various criteria in mammals and by tadpole metamorphosis (Roche and Michel, 1955). In experiments in our laboratory involving radiochromatography, L. B. Hardy, Jr, identified both T-3 and T-4 as components of chicken plasma in 1957 (unpublished data); and in 1958, one of us (B. C. W.) found T-3 and T-4 in both plasma and thyroid extracts from chickens (unpublished data). Shellabarger and Pitt-Rivers (1958) have also isolated both T-3 and T-4 from chicken thyroids.That the relative potencies of T-3 and T-4 might not be the same in the fowl as in mammals was indicated by Shellabarger (1955), who reported that T-3 was no …

The effect of change in chemical structure of some thyroxine analogues on the metamorphosis of Rana pipiens tadpoles.

Forty-three different substances structurally related to tliyroxine were assayed for their metamorphosing effect on Rana pipiens tadpoles. Triiodinated compounds with iodines at the 3,3′,5 positions were found more active than tetraiodinated compounds. The 3,5- and 3,3′ diiodinated compounds tested also had some activity except for the 3,5 diiodothyroformic acid. None of the monoiodinated compounds assayed showed biological activity. The most active compound studied was 3,3′,5-triiodothyropropionic acid which was 300 times more potent that ?-thyroxine. IN 1912 Gudernatsch (1) showed that tadpole metamorphosis was under the control of the thyroid gland. Since these original observations, many iodinated compounds have been reported capable of inducing amphibian metamorphosis. Recently the relationship of thyroxine-like metamorphosing activity and chemical structure of some compounds has been studied by Roche et al.(2) and reviewed by Bruice et al. (3). The recent discovery of naturally occurring thyroxine-l...

Effect of desoxycorticosterone acetate on metamorphosis induced by throxine in anuran tadpoles.

Effects of desoxycorticosterone acetate (DCA) on thyroxine-induced metamorphosis were studied. When tadpoles at hind limb-bud stage are treated with DCA alone, their metamorphosis is completely inhibited. DCA seems to inhibit development of functional activity of the thyroid gland in the tadpoles at this stage. But when thyroxine and DCA are given simultaneously, the steroid accelerates the water loss as well as the following degenerative changes of thyroxine-induced metamorphosis: decrease in the length of trunk and tail, resorption of tail fin and opercular perforation. On the other hand, it antagonizes slightly but significantly the effect of thyroxine on anabolic changes such as the growth of forelegs and hind limbs. It is suggested that the ratio of circulating amounts of thyroxine and mineralocorticoids is important in regulating the metamorphosis of anuran tadpoles.

Sur les activités biologiques des iodothyronines et de divers analogues structuraux des hormones thyroïdiennes

1. 1. Antigoitrogenic activity and its effect on the metamorphosis of tadpoles of Rana esculenta have been studied with sixteen iodothyronines and substances similar in structure to them, in order to determine the role of the position and number of iodate substituents and of the nature of the carbon side chain. 2. 2. The 3:5:3′-iodo-derivatives show themselves to be mor active than their homologues 3:5:3′:5′-tetraiodinated, whether the carbon side chain is an alanine- (iodothyronines), propionic acid- or acryloyl-residue or a carboxyl group. In the iodothyronine series, the dl-3:3′-diiododerivative shows as great an activity as that of the dl-thyroxine. That of the dl-3:3′:5′-triiodothyronine is very small in contrast to that of the dl-3:5:3′-triiodothyronine, previously defined as being five times greater than that of dl-thyroxine. 3. 3. The presence of one atom of iodine at 3 and one at 3′ is necessary condition for the existence of activity; this activity is strengthened by a substitution at 5 and reduced by a substitution at 5′. 4. 4. Its effect on the metamorphosis of tadpoles does not always run parallel with its effect on the development of experimental goitre. This activity is very great in the case of thyropropionic and thyroacryloyl derivatives, and in the case of 3:5:3′-triiodopropionic acid reaches a value 290 times that of DL-thyroxine. 5. 5. The fact that a series of iodothyronines and the thyropyruvic acids derived from them are active products allows a consideration of the problem of the unity or the multiplicity of the substances making up the active form of the physiological hormone.

ハロゲン化カゼインの研究 (第1報)

Bromocasein was prepared in accordance with that for iodocasein and free bromine was eliminated by electrodialysis. The bromine content of bromocasein was 4.0-4.2%. This bromocasein also showed acceleration of tadpole metamorphosis but in a degree far weaker than that of iodocasein.

Antithyroxine properties of n-(2,5 dihydroxyphenyl) pyridinium acetate.

Conclusions(1) N-(2,5-dihydroxyphenyl) pyridinium acetate inhibited the metamorphosis of tadpoles induced by thyroxine. The degree of inhibition of metamorphosis appeared proportional to the relative concentration of the drug. (2) N-(2,5-dihydroxyphenyl) pyridinium acetate, 200 mg/kg body weight, did not lower the rate of oxygen consumption of normal rats nor prevent the acceleration of oxygen consumption induced by dl-thyroxine, 2 mg/kg body weight.

Thyroid hormone-like properties of tetrabromotyronine and tetrachlorothyronine.

ALTHOUGH the important part played by iodine in the action of the thyroid hormone is thoroughly appreciated, its mode of action remains one of the intriguing mysteries of thyroid physiology. Baumann's (1896(1)) discovery of iodine in the thyroid gland, Kendall's (1915(2)) isolation of a substance from the thyroid containing 60 per cent iodine which was capable of abolishing all manifestations of thyroid insufficiency, and the synthesis of crystalline thyroxine by Harington and Barger (1927(3)) are significant landmarks in our increasing knowledge concerning the importance of iodine in thyroid physiology. Harington and Barger concluded from their studies that the physiologic activity of the hormonal compound is dependent upon its content of iodine. Abderhalden and Wertheimer (1928(4)) tested the potency of certain analogs of thyroxine by comparing the effects of these compounds with those of thyroxine on the metamorphosis of tadpoles and axolotls. They found that tetrabromthyronine, a compound in which the...

A contribution to the study of fore‐limb eruption in metamorphosing Anura.

Summary. The fore‐limbs of Xenopus laevis are freed from their brachial sacs at the onset of metamorphosis in response to an endocrine stimulus. The disappearance of the tissues overlying the young limbs is not a result of mechanical pressure exercised by limb growth, nor is it aided by stresses created by changes in head shape during metamorphosis. Mechanical pressure resulting from movements of the limbs hastens their liberation, but the thinning and perforation of the overlying tissues can take place in the experimentally contrived absence of the limb. Metamorphic changes in the branchial chamber, in particular the involution of larval structures, can play no part in initiating the perforation process in this species. It is suggested that the rôle of substances released by degenerating gills in inducing opercular perforation in the normal metamorphosis of other Anuran species has not been satisfactorily established. The process of fore‐limb liberation in the precociously induced metamorphosis of young tadpoles is regarded as essentially similar to the equivalent process in normal metamorphosis. This consideration, taken with the results of some earlier workers, leads to a rejection of the claim that Anurau fore‐limbs are liberated as a consequence of the histolytic properties of the secretion of glands in their skin. The only factor that may be regarded as universally effective in the perforation process is the specificity of the tissues concerned to atrophy in response to endocrine conditions at the onset of metamorphosis. It is suggested that this factor alone is responsible for initiating the process in Xenopus, and probably in other species as well. There is no justification for regarding the process of perforation as an example of double assurance.

DEPIGMENTATION IN RANA TEMPORARIA TADPOLES AS A RESULT OF METHYLTHIOURACIL TREATMENT

The aim of this study originally was to elucidate whether methylthiouracil will cause thyroid hyperplasia and inhibition of metamorphosis in frog tadpoles or not, provided it should prove to be sufficiently non-toxic to be employed experimentally. During the experiments, however, changes in the pigmentation of the larvae also occurred, and it is these observations which are chiefly described in this communication. A study of the literature revealed some communications on related experiments. On the whole agreement exists that most of the substances which are known to be goitrogenic in mammals have the same effect in amphibian larvae [Gordon, Goldsmith & Charipper, 1943; 1945]. However, changes in pigmentation after such treatment are mentioned only by Lynn & De Marie [1946]. These investigators noted inhibition of metamorphosis in Rana sylvatica immersed into 0·05 % thiourea and thiouracil. Animals treated with thiourea did not develop further when reimmersed in water. From the 26th day

Teneur en thyroxine et activité biologique de diverses protéines artificiellement iodées (caséine, insuline, thyroglobuline) et de la thyroglobuline

1. 1. The action of various iodinated proteins (iodocasein, iodoinsulin, iodothyroglobulin), of natural thyroglobulin and of thyroxin on the metamorphosis of tadpoles of Bufo bufo and on experimental goitre in rats fed on a diet containing 6.N-propylthiouracil has been studied under strictly comparative conditions. 2. 2. Iodocaseins prepared by various methods and containing nearly the same thyroxin percentage are of very different activities when administered by mouth; these differences are less marked and can even disappear when the same products are injected or when submitted to tryptic hydrolysis. The biological efficiency of the iodinated proteins, thus, depends not only on their thyroxin content, but also on the assimilation of the hormone. Previous researches have given results interpreted as showing differences in thyroxin content of iodoproteins when an increase of assimilation was obtained. 3. 3. Iodoinsulin and natural thyroglobulin show, per unit weight of thyroxin, a biological activity greater than free thyroxin. The data obtained in this work lead to the conclusion that the hormone present in these proteins is better utilized than free thyroxin, owing to its progressive penetration in the body fluids during the proteolysis.

THE USE OF THIOURACIL IN THE TREATMENT OF PATIENTS WITH HYPERTHYROIDISM

Excerpt HISTORICAL REVIEW The origin of the use of thiouracil in the treatment of hyperthyroidism stems from the past studies of the mechanism of the production of experimental goiter. During the c...

THE RELATIVE THYROIDAL POTENCY OF 1- AND d,1-THYROXINE1

ALTHOUGH it was established by Harington and Salter (1930) that thyroxine naturally occurs in the thyroid in the optically active levo form, there is still considerable uncertainty as to the relative potency of pure 1-thyroxine and the racemic thyroxine that until recently has been the only form readily available for animal experimentation and clinical use. Using compounds prepared by Harington (1928) Gaddum reported that, as tested by the stimulation of tadpole metamorphosis (1927) and rat metabolism (1929-30), 1-thyroxine showed about three times the potency of the d- form. Upon testing the same compounds in human myxedema, Salter, Lerman and Means (1935) found no difference in activity. On the other hand Foster, Palmer and Leland (1936) reported that 1-thyroxine obtained by the enzymatic hydrolysis of thyroid substance exerted twice the effect of a racemic mixture as judged by its calorigenic effect in guinea pigs, and thus inferred that the d- compound is devoid of activity.

INHIBITION OF METAMORPHOSIS IN TADPOLES BY THIOURACIL1

Journal Article INHIBITION OF METAMORPHOSIS IN TADPOLES BY THIOURACIL Get access Endocrinology, Volume 34, Issue 2, 1 February 1944, Pages 138–139, https://doi.org/10.1210/endo-34-2-138 Published: 01 February 1944 Article history Received: 29 November 1943 Published: 01 February 1944

THE PREPARATION AND BIOLOGICAL EFFECTS OF IODINATED PROTEINS

The induction of premature metamorphosis in tadpoles by the administration of thyroid preparations, first shown by Gudernatsch [1914], has been studied from various aspects in a number of Anura, most commonly in one or other species of Rana. Morse [1914] and Rogoff & Marine [1917] noted the reaction of R. pipiens tadpoles to thyroid and other substances, and found that a similar effect could be produced by iodinated blood protein. Lenhart [1915] suggested that the tadpole response could be used for biological assay. Romeis [1923] studied the reaction of tadpoles to thyroxine and di-iodotyrosine in some detail and noted the minimal active doses. Blacher [1928] and Allen [1932], working respectively with tadpoles of Rana and of Bufo, studied the sequence of response of different organs to thyroxine. Alphonse & Baumann [1935] found that Rana temporaria tadpoles with back legs 2 mm. in length responded very rapidly to thyroxine. Kaer [1934]

Stimulation of the Milk Production of Dairy Cows by Feeding Thyroid-active Iodinated Proteins

GRAHAM1, working at the University of Toronto, and afterwards at this Institute2, demonstrated a marked temporary galactopoietic effect of both orally administered dried thyroid gland and subcutaneously injected thyroxine in dairy cows. This has been confirmed both in Great Britain3 and in the United States4. In 1914 Morse5 found that the effects of iodinated proteins on the metamorphosis of tadpoles were comparable to those of thyroid, and more recently (1939) Ludwig and von Mutzenbecher have shown6, and Harington and Pitt Rivers7 have confirmed, that thyroxine can be isolated from hydrolysates of casein treated with iodine (iodinated casein). The possible use of iodinated casein for the stimulation of milk production in the dairy cow was visualized by Bottomley and Folley8, who carried out small-scale experiments with cows9 which indicated that transient increases in milk production could be obtained by feeding iodinated casein.