propylthiouracil and Deficiency-Diseases

Copper (Cu), iron (Fe), and iodine/thyroid hormone (TH) deficiencies lead to similar defects in late brain development, suggesting that these micronutrient deficiencies share a common mechanism contributing to the observed derangements. Previous studies in rodents (postweanling and adult) and humans (adolescent and adult) indicate that Cu and Fe deficiencies affect the hypothalamic-pituitary-thyroid axis, leading to altered TH status. Importantly, however, relationships between Fe and Cu deficiencies and thyroidal status have not been assessed in the most vulnerable population, the developing fetus/neonate. We hypothesized that Cu and Fe deficiencies reduce circulating and brain TH levels during development, contributing to the defects in brain development associated with these deficiencies. To test this hypothesis, pregnant rat dams were rendered Cu deficient (CuD), FeD, or TH deficient from early gestation through weaning. Serum thyroxine (T(4)) and triiodothyronine (T(3)), and brain T(3) levels, were subsequently measured in postnatal d 12 (P12) pups. Cu deficiency reduced serum total T(3) by 48%, serum total T(4) by 21%, and whole-brain T(3) by 10% at P12. Fe deficiency reduced serum total T(3) by 43%, serum total T(4) by 67%, and whole-brain T(3) by 25% at P12. Brain mRNA analysis revealed that expression of several TH-responsive genes were altered in CuD or FeD neonates, suggesting that reduced TH concentrations were sensed by the FeD and CuD neonatal brain. These results indicate that at least some of the brain defects associated with neonatal Fe and Cu deficiencies are mediated through reductions in circulating and brain TH levels.

Topics: Animals; Animals, Newborn; Brain; Copper; Deficiency Diseases; Female; Gene Expression Regulation, Developmental; Iron; Iron Deficiencies; Male; Pregnancy; Propylthiouracil; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thyroid Gland; Thyroid Hormones

Thyroids of rats fed an iodine-deficient diet for several months contain small psammoma bodies within the follicular lumens which concentrate radioactive iodine. If the iodine-deficient rats are fed a high-iodine diet to produce a "colloid goiter" with reaccumulation of PAS-positive colloid around the psammoma bodies before administering radioactive iodine, the radioactivity is present in follicular cells, around the psammoma bodies and in the colloid 24 hours after radioactive iodine administration. Propylthiouracil (PTU) causes radioactivity to disappear from the cells and colloid but does not produce any appreciable discharge of radioactivity from the psammoma bodies. If radioactive iodine is given to the iodine-deficient rats before feeding a high-iodine diet, radioactivity is initially present chiefly in the cells and psammoma bodies and gradually accumulates in the PAS-positive colloid as this becomes deposited under the influence of the increased dietary iodine. If such rats are fed PTU for 4 days before the high-iodine diet is instituted, radioactivity remains limited almost entirely to the psammoma bodies and does not appear in the accumulating colloid. It is concluded that the psammoma bodies are iodinated directly, rather than forming a nidus for condensation of intrafollicular thyroglobulin after it is iodinated. Although iodine is readily bound to the psammoma bodies, it apparently is not easily removed from these structures under in vivo conditions.

Topics: Animals; Colloids; Deficiency Diseases; Iodine; Iodine Radioisotopes; Male; Propylthiouracil; Rats; Thyroid Gland

Topics: Animals; Deficiency Diseases; Diet; Disease Models, Animal; Estradiol; Hyperplasia; In Vitro Techniques; Injections, Intramuscular; Iodine; Mammary Glands, Animal; Propylthiouracil

Topics: Animals; Carbon Isotopes; Centrifugation, Density Gradient; Chemical Phenomena; Chemistry, Physical; Deficiency Diseases; Diet; Hydrogen-Ion Concentration; Iodides; Iodine; Iodine Isotopes; Macromolecular Substances; Male; Metabolism; Osmolar Concentration; Perchlorates; Propylthiouracil; Rats; Sodium; Sucrose; Thyroglobulin

Topics: Animals; Anthracenes; Breast; Breast Diseases; Breast Neoplasms; Deficiency Diseases; Demography; Estrogens; Female; Hypothyroidism; Iodine; Male; Propylthiouracil; Rats

Topics: Autoradiography; Colloids; Deficiency Diseases; Diet; Injections, Intravenous; Iodine; Iodine Isotopes; Propylthiouracil; Thyroid Gland

Topics: Age Factors; Aminopyrine; Aniline Compounds; Animals; Benzoates; Benzopyrenes; Biotransformation; Cytochromes; Deficiency Diseases; Hexobarbital; Hypothyroidism; Iodides; Iron; Mice; Microsomes, Liver; Nitrophenols; Propylthiouracil; Riboflavin; Riboflavin Deficiency; Sleep; Time Factors

Topics: Animals; Biological Transport, Active; Cell Membrane Permeability; Computers; Deficiency Diseases; Depression, Chemical; Iodides; Iodine; Iodine Isotopes; Kinetics; Male; Models, Biological; Propylthiouracil; Rats; Thiocyanates; Thyroid Gland

The present studies demonstrate that iodine depletion increases the sensitivity of the thyroid to the goitrogenic effects of thyrotropin. Iodine depletion was induced by feeding rats a low iodine diet containing propylthiouracil for 10-14 days before hypophysectomy. Accumulation of iodine in the thyroid after hypophysectomy was prevented by continuing the antithyroid drugs in the diet. Doses of thyrotropin as low as 3 mU/100 g of body weight per day produced significant thyroid enlargement in 3-7 days in iodine-depleted rats. Adding propylthiouracil or perchlorate to the diet during treatment with thyrotropin did not reduce or augment the goitrogenic response to thyrotropin in iodine-depleted rats. Increasing the level of circulating iodide also did not reduce the goitrogenic response to thyrotropin. The increased sensitivity of the iodine-depleted thyroid gland may provide an explanation for the development of thyroid enlargement without requiring an increased level of circulating thyrotropin.

Topics: Animals; Deficiency Diseases; Diet; Goiter; Hypophysectomy; Iodine; Perchlorates; Pituitary Gland; Propylthiouracil; Rats; Thyroid Gland; Thyrotropin

Topics: Animals; Chromatography, Paper; Deficiency Diseases; Diiodotyrosine; Iodides; Iodine; Iodine Isotopes; Iodoproteins; Male; Monoiodotyrosine; Perchlorates; Propylthiouracil; Rats; Thyroid Gland; Thyroxine; Triiodothyronine; Tyrosine

Topics: Animals; Deficiency Diseases; Feedback; Goiter; Hyperplasia; Iodine; Iodine Isotopes; Iodoproteins; Male; Perchlorates; Propylthiouracil; Rats; Thyroid Hormones; Thyrotropin

Topics: Animals; Blood; Deficiency Diseases; Diiodotyrosine; Iodides; Iodine; Male; Monoiodotyrosine; Perfusion; Propylthiouracil; Rats; Thyroid Gland; Thyroxine; Triiodothyronine

Topics: Animals; Colloids; Deficiency Diseases; Diet; Female; Goiter; Hyperplasia; Iodine; Male; Organ Size; Propylthiouracil; Rats; Thyroglobulin; Thyroid Gland; Thyrotropin

Topics: Animals; Deficiency Diseases; Diiodotyrosine; Humans; Iodine; Perchlorates; Propylthiouracil; Rats; Substance Withdrawal Syndrome; Thyroid Gland; Thyroxine; Triiodothyronine; Tyrosine