Propylthiouracil

About: Propylthiouracil is a research topic. Over the lifetime, 2181 publications have been published within this topic receiving 46996 citations. The topic is also known as: Thyreostat® & 2,3-dihydro-6-propyl-2-thioxo-4(1H)-pyrimidinone.

Postnatal development of pulmonary alveoli: modulation in rats by thyroid hormones

Abstract: We studied the effect of thyroid hormones on the postnatal development of the gas exchange region of rat lungs. Treatment with triiodothyronine (T3, 0.1 microgram . g body wt-1 . day-1) accelerated the increase of the surface-to-volume ratio (S/V) and surface area (Sa) and decrease of the mean chord length (Lm) of the gas exchange structures of pups killed at age 7 days. Propylthiouracil (PTU, 100 micrograms twice daily) from age 1 to 13 days, with death at age 14 days, diminished the rise of S/V and Sa and the fall of Lm compared with diluent-injected pups. Providing drinking water with 0.01% PTU to dams from gestation day 20 (term 22 days) to postnatal day 14 also diminished the rise of S/V and fall of Lm. Treatment of pups nursed by dams drinking 0.01% PTU with thyroxine (0.1 microgram/g body wt) every other day from age 1 to 13 days significantly diminished the effect of PTU on S/V, Sa, and Lm. We conclude thyroid hormones can modulate the postnatal architectural development of the gas exchange region of the rat lung.

Growth hormone, somatomedin and cartilage sulfation in failure of catch-up growth after propylthiouracil-induced hypothyroidism in the rat.

Abstract: Male Long-Evans rats 36 to 39 days of age were fed a diet containing 0.1% propylthiouracil (PTU) for 17 to 20 days followed by the resumption of normal diet. Growth rates of body weight and tail length decreased during PTU treatment and increased during recovery; yet only slight catch-up (compensatory) growth occurred in either body weight or tail length. Although serum thyroxine and triiodothyronine concentrations (radioimmunoassay) decreased significantly during PTU treatment, they returned to normal by recovery day 14. Pituitary immunoassayable growth hormone (GH) content and concentration dropped during PTU-feeding. By recovery day 14 there was significant, but incomplete, repletion of the gland. Serum GH during ether anesthesia was increased significantly during PTU treatment; it remained elevated (NS) and showed greater variability during recovery than in controls. Bioassayable serum somatomedin (Sm) activity decreased during PTU treatment in one of two experiments but returned to a normal level by ...

Obligatory role of thyroid hormones in development of peripheral sympathetic and central nervous system catecholaminergic neurons: effects of propylthiouracil-induced hypothyroidism on transmitter levels, turnover and release.

Abstract: Thyroid status is thought to play a major role in establishing the time course of development of sympathetic nerve pathways. Hypothyroidism induced by perinatal administration of propylthiouracil to developing rats resulted in substantial deficits in cardiac norepinephrine levels that persisted into adulthood. This shortfall was not accompanied by compensatory receptor supersensitivity or by increased utilization of remaining transmitter. Indeed neonatal hypothyroidism is known to result in end-organ subsensitivity and the norepinephrine turnover rate, an index of spontaneous activity of the neuron, was found to be markedly subnormal. The ability of cardiac sympathetic neurons to release transmitter upon pharmacological challenge was also compromised by hypothyroidism: in control neonates, administration of tyramine resulted in displacement of norepinephrine from nerve terminals, a response which was present very early in development. Hypothyroid rats did not develop the ability to release transmitter in response to tyramine until 10 days postnatally and a fully mature response was not apparent until weeks later. Ontogeny of the capability to release norepinephrine in response to hypotension (baroreflex) also was assessed through administration of hydralazine, a direct arteriolar vasodilator; control rats showed a characteristic development of this response at the end of the 2nd postnatal week, whereas hypothyroid rats did not show any potential for norepinephrine release until young adulthood (41 days). In comparison to cardiac sympathetic neurons, an overall evaluation of central catecholaminergic pathways in whole brain indicated a much smaller effect of hypothyroidism, with no (norepinephrine) or only minor (dopamine) deficits in transmitter content and smaller, transient reductions in turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Neonatal hepatitis and lymphocyte sensitization by placental transfer of propylthiouracil

Abstract: A female newborn whose mother was taking propylthiouracil (PTU) for Graves' disease, presented with transient thyrotoxicosis (serum triiodothyronine 1,710 ng/dl) and signs of acute hepatic injury. Jaundice and choluria were evident on her fourth day of life. Serum total bilirubin reached 14 mg/dl, with a direct fraction of 11 mg/dl. Serum alanine aminotransferase and aspartate aminotransferase showed moderate elevations (110 IU/l and 61.5 IU/l, respectively), as well as the alkaline phosphatase which increased to about twice the upper limit of normal. When incubated with PTU, the patient's cultured peripheral lymphocytes underwent transformation to more than twice the values found in 2 controls, with a stimulation index (SI) of 3.19, compared to SI of 1.45 and 1.15 for the controls, suggesting a hypersensitivity mechanism involved in the hepatic injury. Although about 20 cases of PTU induced hepatic damage were reported in the medical literature, this is, as far as we know, the first description of neonatal liver injury probably caused by placental transfer of this drug.

Increase in the Number of Type II Insulin-Like Growth Factor Receptors during Propylthiouracil-Induced Hyperplasia in the Rat Thyroid

Abstract: We have observed that membranes isolated from rat thyroids contain receptors for the insulin-like growth factors (IGF). As IGFs are known to be important mediators of tissue growth, we conducted this study to determine whether modulation of thyroid IGF receptors might be involved in TSH-stimulated hyperplasia. A substantial increase in both the weight of the thyroid and its DNA content was observed within 2 days of exposing adult male rats to 0.1% propylthiouracil (PTU) in their drinking water. Serum T4 reached unmeasurable levels and serum TSH rose 3-fold over control by the tenth day of treatment. [125I]Iodo-human(h)IGF-II binding to membranes isolated from hyperplastic glands was significantly higher than control beginning at 2 days. A maximum was reached after 5 days (13.3 ± 0.8%/25 ng protein us. a control level of 6.7 ± 0.7%, mean ± SEM). The increase had disappeared by 15 days of PTU exposure, paralleling the drastic fall in the growth rate of the glands. This increase in binding was specific for t...