thiouracil and Congenital-Hypothyroidism

The aim of this study was to investigate the potential relationship between hypothyroidism and delta-aminolevulinate dehydratase (delta-ALA-D) activity in rat blood and liver. Experimental hypothyroidism was induced in weanling rats by exposing their mothers to propylthiouracil (PTU) diluted in tap water (0.05% w/ v), ad libitum, during the lactational period (PTU group). Control (euthyroid) group included weanling rats whose mothers received just tap water, ad libitum, during the lactational period. Reverted-hypothyroid group (PTU + 3,3',5-triiodo-L-thyronine [T(3)]) included weanling rats whose mothers were exposed to PTU similarly to those in the hypothyroid group, but pups received daily subcutaneous injections of T(3) (20 microg/kg, from Postnatal Days 2-20). After the treatment, serum T(3) levels were drastically decreased (around 70%) in the PTU group, and this phenomenon was almost reverted by exogenous T(3). PTU decreased blood delta-ALA-D activity by 75%, and T(3) treatment prevented such phenomena. Erythrocytes and hemoglobin levels were increased by 10% in PTU-treated animals and higher increments (around 25%) were observed in these parameters when exogenous T(3) was coadministered. Dithiothreitol did not change blood delta-ALA-D activity of PTU-exposed animals when present in the reaction medium, suggesting no involvement of the enzyme's essential thiol groups in PTU-induced delta-ALA-D inhibition. PTU did not affect blood delta-ALA-D activity in vitro. These results are the first to show a correlation between hypothyroidism and decreased delta-ALA-D activity and point to this enzyme as a potential molecule involved with hypothyroidism-related hematological changes.

Topics: Animals; Animals, Newborn; Antithyroid Agents; Congenital Hypothyroidism; Disease Models, Animal; Dithiothreitol; Enzyme Activation; Erythrocytes; Female; Hemoglobins; Lactation; Liver; Male; Porphobilinogen Synthase; Rats; Rats, Wistar; Thiouracil; Triiodothyronine

The important influence of postnatal thyroid status on development is well recognized, while the effect of prenatal thyroid status on postnatal growth is less understood. The present study was undertaken to assess the effects of pre- and postnatal thiouracil administration on postnatal growth and pituitary grown hormone (GH) content in 25 day old rats. Pups were born to Sprague-Dawley rats fed lab chow mash containing 0.25% thiouracil according to the following schedules: a) during gestation only; b) during lactation only (25 days postpartum); and c) through gestation and lactation. Mothers of euthyroid controls were fed diet without thiouracil for the length of the experiment. Pups were weighed daily through day 21 and decapitated on day 25. Pituitary GH content was measured by densiometric comparison of disc gel column electrophoresed pituitary homogenates with similarly treated rat GH standard. Incorporation of thiouracil into the diet of pregnant and/or lactating rats significantly depressed the body weight and pituitary GH levels in their 25 day old pups. Furthermore, analysis of the daily mean body weight of each litter revealed four significantly different patterns of growth. While previous investigators have reported that prenatal thyroid restriction does not significantly alter the developmental processes of young rodents, the present study indicates that prenatal thyroid status is an important influence on normal postnatal growth.

Topics: Analysis of Variance; Animals; Congenital Hypothyroidism; Female; Growth Hormone; Organ Size; Pituitary Gland; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Inbred Strains; Thiouracil; Thyroid Gland

Behavioral deficits in adult rats exposed perinatally to thiouracil were substantially reduced or elimated by a 5-week period of "superenriched" postweaning rearing conditions before testing. This treatment resulted in remediation of hypothyroid rats' deficits in maze learning, maze retention, and resistance to extinction of bar-pressing; the facilitative effect persisted for more than 4 months. These behavioral results were consistent with neurohistological findings from studies of early thyroid deficiency and postweaning environmental stimulation in rats.

Topics: Age Factors; Animals; Congenital Hypothyroidism; Disease Models, Animal; Environment; Extinction, Psychological; Female; Hypothyroidism; Learning; Pregnancy; Rats; Retention, Psychology; Thiouracil

Topics: Animals; Behavior, Animal; Birth Weight; Body Weight; Congenital Hypothyroidism; Dose-Response Relationship, Drug; Female; Humans; Hypothyroidism; Learning Disabilities; Litter Size; Male; Maternal-Fetal Exchange; Pregnancy; Rats; Thiouracil; Thyroid Gland; Time Factors

Topics: Adrenal Gland Neoplasms; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Congenital Hypothyroidism; Cushing Syndrome; Female; Glucocorticoids; Goiter; Humans; Hydrocortisone; Hyperparathyroidism; Hyperthyroidism; Hypocalcemia; Hypoparathyroidism; Infant, Newborn; Iodine; Maternal-Fetal Exchange; Parathyroid Diseases; Pregnancy; Thiouracil; Thyroid Hormones

Topics: Congenital Hypothyroidism; Thiouracil

Topics: Animals; Brain; Carbonic Anhydrases; Congenital Hypothyroidism; Neurochemistry; Rats; Thiouracil