thiourea and Goiter

Topics: Aminosalicylic Acids; Animals; Antithyroid Agents; Bromides; Chickens; Deficiency Diseases; Disease Models, Animal; Fluorides; Goiter; Guinea Pigs; Humans; Iodine; Lithium; Mice; Rats; Resorcinols; Sulfonylurea Compounds; Thiocyanates; Thiourea; Thyroid Gland

Studies on the role of thyroid hormones (THs) in teleost fish physiology have deployed the synthetic goitrogens, methimazol (MMI), propilthiouracil (PTU) and thiourea (TU) that are used to treat human hyperthyroidism. However, the action of the goitrogens, MMI, PTU and TU at different levels of the hypothalamic-pituitary-thyroid (HPT) axis in teleosts is largely unknown. The central importance of the hypothalamus and pituitary in a number of endocrine regulated systems and the cross-talk that occurs between different endocrine axes makes it pertinent to characterize the effects of MMI, PTU and TU, on several endpoints of the thyroid system. The marine teleost, sea bream (Sparus auratus) was exposed to MMI, PTU and TU (1mg/kg wet weight per day), via the diet for 21days. Radioimmunoassays (RIA) of plasma THs and ELISA of the TH carrier transthyretin (TTR) revealed that MMI was the only chemical that significantly reduced plasma TH levels (p<0.05), although both MMI and PTU significantly (p<0.05) reduced plasma levels of circulating TTR (p<0.05). Histological analysis of the thyroid tissue revealed modifications in thyrocyte activity that explain the reduced circulating levels of THs. MMI also significantly (p<0.05) up-regulated transcript abundance of liver deiodinase 1 and 2 while significantly (p<0.05) decreasing TRβ expression in the pituitary, all hallmarks of HPT axis action of goitrogens in vertebrates. The results indicate that in the sea bream MMI is the most effective goitrogen followed by PTU and that TU (1mg/kg wet weight for 21days) failed to have a goitrogenic effect. The study highlights the non-uniform effect of goitrogens on the thyroid axis of sea bream and provides the basis for future studies of thyroid disrupting pollutants.

Topics: Animals; Goiter; Methimazole; Phenylthiourea; Prealbumin; Radioimmunoassay; Sea Bream; Thioamides; Thiourea; Thyroid Gland; Thyroid Hormones

N,N,N',N'-Tetramethylthiourea (TMTU) is a rat goitrogen inducing thyroid hyperplasia, hypertrophy, and tumor formation. Little is known about the exact underlying mechanism of action. As thyroid peroxidase (TPO) and type I iodothyronine deiodinase (ID-I) have been established as targets of goitrogenic thiourea derivatives, we investigated interactions of TMTU with target enzymes using a partially purified fraction from hog thyroids or solubilized hog thyroid microsomes and 10,000g supernatant from rat liver homogenate, respectively, as enzyme sources. For comparison, comprehensively characterized goitrogenic thiourea derivatives were studied as well. In contrast to propylthiouracil (PTU), and like ethylenethiourea (ETU), TMTU only marginally affected TPO-catalyzed oxidation of guaiacol. TMTU, like ETU, concentration-dependently suppressed TPO-catalyzed iodine formation with concomitant oxidative metabolism. Suppression ceased upon consumption of thiourea derivatives, the rate of the reappearing iodine formation was similar to that of controls. TMTU, like ETU, also suppressed non-enzymatic and TPO-catalyzed monoiodination of l-tyrosine with a stoichiometry of 2:1, i.e., one molecule of thiourea derivative suppressed two times monoiodination. TMTU and ETU were unable to irreversibly inhibit TPO. In contrast to PTU, TMTU did not inhibit ID-I. These findings provide evidence that TMTU interferes with thyroid hormone synthesis at the level of iodination and demonstrate a metabolic route for the oxidative detoxification of TMTU in the thyroid suggesting that low-level or intermittent exposure to TMTU would have only minimal effects on thyroid hormone synthesis. Finally, it can be concluded that meaningful toxicological studies on TPO inhibition can be performed without a need for highly purified TPO.

Topics: Amitrole; Animals; Antithyroid Agents; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Enzyme Inhibitors; Ethylenethiourea; Goiter; Guaiacol; Hydrogen Peroxide; Iodide Peroxidase; Iodine; Oxidation-Reduction; Propylthiouracil; Rats; Swine; Thiourea; Time Factors; Tyrosine

1. Goitrogenic action of methallibure (ICI-33828) has been studied in mice gerbil and hedgehog using thyroid weight and histological structure as an index. Liquefaction and vacuolation of thyroid follicles were most prevelant after methallibure administration. 2. The I131 content of the thyroid gland was significantly higher in the methallibure treated groups than in the controls. This denotes a decrease in the rate of discharge of thyroid hormone. 3. Protein bound radioiodine (Pb I131) was low after methallibure administration. 4. Methallibure administration brings about hypertrophy of pituitary thyrotrophs which is also reflected in the increased basophilic cell percentage in gerbil (control: 15.5 percent; methallibure: 22.8 percent). 5. It is concluded that methallibure acts on thyroid function both by a direct effect on the gland as well as by influencing pituitary thyrotrophic activity in enhancing I131 uptake.

Topics: Animals; Cell Count; Gerbillinae; Goiter; Hedgehogs; Iodine; Iodine Radioisotopes; Male; Methallibure; Mice; Pituitary Gland; Thiourea; Thyroid Function Tests; Thyroid Gland

Topics: Animals; Animals, Newborn; Antithyroid Agents; Diet; Disease Outbreaks; Food Analysis; Goiter; Humans; Hyperthyroidism; Rabbits; Sheep; Sheep Diseases; Thiocyanates; Thiourea

Topics: Abnormalities, Drug-Induced; Adult; Age Factors; Androgens; Bone Diseases; Cobalt; Congenital Hypothyroidism; Contraceptives, Oral; Deficiency Diseases; Endocrine System Diseases; Environmental Pollutants; Estrogens; Female; Fetus; Genitalia, Female; Goiter; Humans; Infant; Infant, Newborn; Iodine; Male; Maternal-Fetal Exchange; Pregnancy; Progesterone; Thiocyanates; Thiourea; Transposition of Great Vessels

Topics: Azides; Chemical Phenomena; Chemistry; Dimethyl Sulfoxide; Goiter; Heterocyclic Compounds; Imides; Iodine; Kinetics; Models, Biological; Nitrogen; Phthalic Acids; Spectrophotometry, Ultraviolet; Structure-Activity Relationship; Succinimides; Thiouracil; Thiourea; Thyroid Gland; Time Factors

Topics: Abnormalities, Drug-Induced; Adrenal Glands; Allyl Compounds; Animals; Animals, Newborn; Bone Development; Chemical and Drug Induced Liver Injury; Female; Goiter; Hematopoiesis; Hernia; Hernia, Diaphragmatic; Hindlimb; Joints; Kidney; Male; Organ Size; Ovarian Follicle; Pregnancy; Radiography; Skin Abnormalities; Skull; Swine; Swine Diseases; Testis; Thiourea

Topics: Abnormalities, Drug-Induced; Animals; Body Weight; Brain; Diencephalon; Female; Fetus; Gestational Age; Goiter; Hypophysectomy; Hypothalamus; Maternal-Fetal Exchange; Organ Size; Pituitary Gland; Pregnancy; Propylthiouracil; Rats; Thiourea; Thyroid Gland; Thyrotropin-Releasing Hormone; Vitamin A

Topics: Animals; Goiter; Pituitary Gland; Thiourea; Thyroidectomy; Thyrotropin; Transplantation, Autologous; Urodela

Topics: Animals; Anura; Colloids; Goiter; Microscopy, Electron; Perchlorates; Thiocyanates; Thiouracil; Thiourea

Topics: Adolescent; Adult; Antithyroid Agents; Blood Cell Count; Diagnosis, Differential; Diagnostic Errors; Female; Goiter; Heart Auscultation; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methylthiouracil; Myxedema; Nervous System Diseases; Neurotic Disorders; Propylthiouracil; Radioisotope Dilution Technique; Thiazoles; Thiouracil; Thiourea; Thyrotropin

Topics: Adolescent; Adult; Child; Chromatography, Paper; Congenital Hypothyroidism; Deficiency Diseases; Female; Goiter; Humans; Iodine; Iodine Radioisotopes; Iodoproteins; Myxedema; Sulfur Isotopes; Thiourea; Thyroid Hormones

Topics: Adolescent; Child; Deafness; Female; Goiter; Humans; Iodine; Iodine Radioisotopes; Male; Metabolism, Inborn Errors; Sulfur Isotopes; Thiourea

Topics: Adolescent; Child; Ethnicity; Goiter; Goiter, Endemic; Humans; Netherlands; Phenylthiourea; Physiology; Taste; Thiourea

Topics: Blood Chemical Analysis; Chromatography; Geriatrics; Goiter; Hyperthyroidism; Iodine Isotopes; Monoiodotyrosine; Myxedema; Neoplasms; Propylthiouracil; Thiourea; Thyronines; Thyroxine; Tyrosine

Topics: Genetics, Medical; Goiter; Humans; Hyperthyroidism; Hypothyroidism; Japan; Nuclear Warfare; Phenylthiourea; Taste; Thiourea; Thyroid Neoplasms; Thyroiditis

Topics: Antithyroid Agents; Exophthalmos; Goiter; Graves Disease; Humans; Hyperthyroidism; Iodine Isotopes; Methylthiouracil; Perchlorates; Radiotherapy; Thiouracil; Thiourea; Thyroidectomy

Topics: Animals; Body Temperature Regulation; Cold Temperature; Fishes; Goiter; Hot Temperature; Hypothyroidism; Research; Temperature; Thiourea; Thyroid Gland; Thyroxine

Topics: Genetics, Medical; Goiter; Humans; Taste; Thiourea

Topics: Goiter; Neoplasms; Thiourea; Thyroid Gland; Thyroid Neoplasms

Topics: Diabetes Mellitus; Goiter; Humans; Phenylthiourea; Taste; Thiourea

Topics: Electrocardiography; Exophthalmos; Goiter; Graves Disease; Humans; Thiouracil; Thiourea

Topics: Goiter; Goiter, Endemic; Iodides; Iodine; Thiouracil; Thiourea

Topics: Goiter; Halogens; Iodides; Iodine; Iodine Isotopes; Thiouracil; Thiourea

Topics: Goiter; Humans; Propylthiouracil; Thiourea

Topics: Exophthalmos; Goiter; Graves Disease; Thiouracil; Thiourea

Topics: Endocrine System Diseases; Goiter; Musculoskeletal Diseases; Thiouracil; Thiourea; Thyroid Gland

Topics: Goiter; Thiouracil; Thiourea; Thyrotoxicosis

Topics: Exophthalmos; Goiter; Graves Disease; Thiouracil; Thiourea; Thyrotoxicosis

Topics: Exophthalmos; Goiter; Graves Disease; Humans; Propylthiouracil; Thiourea

Topics: Goiter; Hypertrophy; Thiourea; Thyroid Gland

Topics: Animals; Goiter; Neoplasms; Rats; Thiourea; Thyroid Gland; Thyroid Neoplasms

Topics: Animals; Goiter; Rats; Thiourea; Thyroid Neoplasms

Topics: Antithyroid Agents; Goiter; Thiouracil; Thiourea

Topics: Goiter; Humans; Hyperthyroidism; Thiouracil; Thiourea; Thyroid Gland

Topics: Goiter; Hyperplasia; Methylthiouracil; Pharmaceutical Preparations; Thiouracil; Thiourea; Thyroid Gland

Topics: Goiter; Humans; Pyrimidines; Thiourea; Thyroid Gland