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At least 811 records · Page 45Linked to original sources
PubMed1978

Opposite variations in serum T3 and reverse T3 during propylthiouracil treatment of thyrotoxicosis.

Blood samples for determination of serum total and free reverse triiodothyronine (rT3), triiodothyronine (T3) and thyroxine (T4) were obtained daily in 6 previously untreated thyrotoxic patients during periods of propylthiourazil (PTU) (600 mg per day) or methimazol (MMI) (45 mg per day) administration. PTU induced about 60 per cent increase in both total and free serum rT3. This was accompanied by a rapid decrease in serum T3 and a more gradual decline in serum T4. MMI administration to untreated patients was followed by a gradual parallel decrease in rT3, T3 and T4. Turn from PTU to MMI produced a rapid decrease in serum rT3 and increase in serum T3 in all 6 patients. The relative variations in the free and total concentrations of iodothyronines were practically identical. The increase in serum rT3 after PTU is most likely explained either by enhanced deiodination of T4 to rT3 or by an inhibitory effect of PTU on rT3 degradation.

Adult↗
PubMed1979

Depletion of colloid 27S and larger thyroid iodoproteins following treatment with propylthiouracil.

By means of a micropuncture technique and microgel electrophoresis the luminal content of single rat thyroid follicles were analyzed during PTU treatment for 4 weeks. The relative amount of aggregates of thyroglobulin (i.e. the 27S iodoprotein and larger complex) was reduced from 15 per cent to approximately 3 per cent after 48 h. The aggregates were practically absent after 2 weeks. The thyroglobulin fraction was the predominant colloid constituent. The protein concentration of the colloid was not changed at the end of the period of PTU treatment (8.9 g/100 ml). It is concluded that PTU inhibits the aggregation of thyroglobulin to a larger complex. The results further indicate that the aggregates of thyroglobulin are preferentially localized to the periphery of the lumen in the larger follicles.

Animals↗
PubMed1980

Effects of propylthiouracil and methylmercaptoimidazole on thyroglobulin synthesis.

The effect of 6-propyl-2-thiouracil (PTU), and 1-methyl-2-mercaptoimidazole (MMI) on thyroglobulin (Tg) biosynthesis has been studied in vivo and in vitro. In vivo experiments were performed in rats treated for 20 days with PTU or MMI, analyzing soluble and particulate, cold and 125I-labelled, Tg. Thyroglobulin biosynthesis was also investigated by in vitro experiments, incubating thyroid tissue with labelled amino acid and carbohydrate in the presence of antithyroid compounds. It has been found that in vivo antithyroid agents decrease the amount of soluble Tg and increase the proportion of particulate Tg. Tg from treated animals is poorly iodinated being mainly represented by its 12S subunit. In vitro studies demonstrate that PTU and MMI inhibit Tg biosynthesis which is impaired in the polypeptide synthesis as well as in carbohydrate chains addition. Thus the inhibition of the hormonogenetic processes induced by antithyroid treatment leading to a depressed iodinating activity also appears to be related to a significant impairment of the production of the Tg molecule, the specific iodine acceptor.

Amino Acids↗
PubMed1983

Effects of KClO4 in propylthiouracil-hypothyroid rats.

In this study we investigated further the antigoitrogenic effect of ClO4 in rats on a low iodine diet (LID) and 6-propyl-2-thiouracil (PTU). The thyroid weight of rats on the mixed goitrogen was initially similar to that of animals on PTU, decreasing to values obtained in rats treated with ClO4 alone by 10 days. Despite the differences in thyroid weight, rats treated during an identical period with PTU or mixed goitrogen develop hypothyroidism to a comparable degree as far as can be assessed by the thyroidal 127I content, plasma T4, T3 and TSH concentrations, and pituitary TSH content. Moreover, it was observed that there were differences in plasma insulin and glucose levels in these hypothyroid animals. The plasma insulin and glucose levels of rats on PTU are comparable to those found in control rats. In rats on mixed goitrogen, both plasma insulin and glucose levels are initially maintained within the normal ranges, and then decline over the subsequent days of treatment. Within the treatment period studied here, plasma insulin and glucose levels were higher for rats on PTU than for animals on ClO4, PTU + ClO4, or thyroidectomized (Th) animals. We have obtained further evidence of the hypothyroid state of rats on these goitrogen regimens based on measurements of pituitary and plasma GH levels and liver mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD). The PTU-treatment decreased the liver alpha-GPD activity to a comparable degree to that of mixed goitrogen. Moreover, both PTU + ClO4 and PTU-treatment resulted in a state of hypothyroidism intense enough to induce effects on growth, and plasma and pituitary GH levels comparable to that of Th animals. However, the values for rats on mixed goitrogen appear to be below the PTU data. The present findings appear to be consistent with the view that TSH is not the unique factor determining the size of the resulting goitre. The results are discussed in relation to the hypothesis that: 1) the antigoitrogenic effect of ClO4 could be associated with changes in the ability of the thyroid tissue to bind TSH, or with a step beyond TSH binding, and 2) the different endocrine and metabolic states of rats on PTU or PTU + ClO4, shown by their different plasma insulin, GH and glucose levels, may play an important role in determining the thyroid weight response to TSH.

Animals↗
PubMed1983

The effect of propylthiouracil and methimazole on the peripheral conversion of thyroxine to 3,5,3'-triiodothyronine in athyreotic thyroxine-maintained rats.

The effect of prolonged oral administration of PTU and MMI on the local conversion of T4 to T3 was studied in T4-maintained athyreotic rats. For this purpose the rats were equilibrated with [125I]T4 and [131I]T3 by means of continuous iv infusions. PTU treatment reduced the MCR of both T4 and T3, as well as the T3 levels in plasma, muscle, liver, kidney and cerebellum. In the cerebral cortex the total intracellular T3 concentration was not affected, while in the pituitary it even increased. The amount of T3 derived from local conversion of T4 to T3 (LcT3(T4)) was reduced in the liver. PTU treatment did not influence Lc T3(T4) in the cerebellum, but did cause an increase in the amount of T3 derived from this source in the cerebral cortex and the pituitary gland (both the homogenate and the nuclear fraction). The results indicate that in contrast to that in liver, local T3 production in the brain and pituitary must occur predominantly via a pathway which is not inhibited by PTU. In MMI-treated rats the total T3 concentration in the cerebral cortex and cerebellum was not altered, whereas both the MCR of T3 and the T3 levels in plasma and various other tissues were elevated. The relative contribution of Lc T3(T4) increased in liver and was reduced in the cerebral cortex, cerebellum and pituitary gland. In all experiments in liver the contribution of Lc T3(T4) to nuclear T3 was negligible, whereas this was not the case for the other hepatic subcellular fractions. As in liver, virtually all renal nuclear T3 was derived from plasma. The present findings suggest that the production of T3 in liver and kidney, and its subsequent release into the blood, may provide a mechanism for the regulation of plasma T3 levels but is not a direct source of their nuclear T3. In the pituitary gland and the brain local T4 to T3 conversion functions as a source of T3 for the control of local utilization. In this respect the maintainance of constant T3 levels in the brain might be important. These differences among tissues suggest that different mechanisms are involved in T4 5'-deiodination.

Animals↗
PubMed1993

Increased testis growth and sperm production in adult rats following transient neonatal goitrogen treatment: optimization of the propylthiouracil dose and effects of methimazole.

Treatment of male rat pups with the reversible goitrogen 6-propyl-2-thiouracil (PTU), administered by adding 0.1% PTU to the mother's drinking water from birth to day 25, increases their testis size and daily sperm production (DSP) at 160 days of age by up to 80% and 140%, respectively. The purpose of this study was to examine the effectiveness of various concentrations of PTU and determine the PTU dose that would maximize testis growth while minimizing side effects such as decreased maternal water consumption and decreased pup growth. Whether this effect was specific to PTU was determined by evaluating the effects of another commonly used goitrogen, methimazole (MMI), in increasing adult testis size and sperm production. Dams were given PTU (0.1-0.0004% w/v) or 0.025% MMI (w/v) in their water from birth to day 25 post partum, then given no further treatment. Thyroxine concentrations were measured in all groups of pups at 25, 35 and 45 days, and testis weight and DSP were determined at 90 days of age. At 25 days of age, thyroxine concentrations were maximally decreased by PTU treatments of 0.0015% or greater; less severe decreases were produced by 0.0004% PTU or 0.025% MMI. Thyroxine concentrations increased in all treated groups at day 35 compared with day 25, and returned to normal by day 45. At 90 days of age, testis weight was increased by about 40% in rats whose mothers had been treated with doses of 0.006% PTU or greater, whereas testis weights in groups given 0.0015 and 0.0004% PTU or 0.025% MMI were increased 31, 15 and 18%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effects of neonatal administration of the reversible goitrogen propylthiouracil on the testis interstitium in adult rats.

The effects of neonatal treatment with the reversible goitrogen, 6-n-propyl-2-thiouracil (PTU) on the volumes of testicular interstitial components, the number and average volume of Leydig cells, and the steroid secretory capacity of testis and Leydig cells of rats at 135 days of age were investigated. Rat pups were hypothyroid from birth to 25 days of age following the addition of 0.1% (w/v) PTU to the drinking water of the mother. Treatment was stopped at 25 days and the pups subsequently returned to a euthyroid state. Control rat pups were raised without adding PTU to drinking water of the mother. On day 135, one testis from each rat (n = 5 per group) was fixed by whole body perfusion for microscopy and stereology, and the ipsilateral testis was used for steroid secretion analysis using an in vitro testis perfusion system. Average testis volume was 84% greater in PTU-treated rats than in controls. This increase resulted from increases in both the seminiferous tubule (86%) and the interstitial (80%) volumes. Moreover, absolute volumes of all testis components in PTU-treated rats were significantly (P < 0.05) greater than those of controls; the highest volume increase was observed in the lymphatic space (147%). The number of Leydig cells per testis was nearly doubled, but the average volume of a Leydig cell was decreased by 25% in PTU-treated rats compared with controls. Steroid secretion per testis was not significantly different between control and PTU-treated rats; however, steroid secretion per Leydig cell was significantly lower in PTU-treated rats than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗