PTU-induced Hypothyroidism Research Articles

Glycogenolytic and hypolipidemic effect of clofibrate (CPIB) in the hypothyroid chick

1. The effect of oral clofibrate (CPIB) administration on carbohydrate and lipid metabolism was investigated in the euthyroid and propylthiouracil (PTU)-induced hypothyroid chick. 2. PTU-feeding significantly increased liver weight, liver glycogen and triglycerides (TG), but decreased liver cholesterol (Ch) and phospholipids (PL). 3. Plasma TG, Ch and PL were significantly elevated in PTU-treated chicks. 4. With PTU-induced hypothyroidism, bile acids concentration in gallbladder bile was increased while those of Ch and PL were decreased. 5. Clofibrate administration to PTU-fed chicks reversed the hypothyroid changes in plasma, liver and biliary lipids. 6. Although CPIB significantly decreased the elevated hepatic glycogen concentration, it did not reverse the significantly decreased glucose-6-phosphatase activity of the hypothyroid chicks. 7. Our results demonstrate that CPIB has both glycogenolytic and hypolipidemic effects. Its action does not seem to be mediated by thyroid hormones and possibly involves changes in pancreatic glucagon and insulin secretion.

220 EFFECT OF THYROID HORMONE ON TISSUE NERVE GROWTH FACTOR (NGF) CONCENTRATIONS IN THE MOUSE

NGF is a protein which has a wide tissue distribution in the mouse and is able to stimulate growth, maturation, and function of autonomic neurons. Because thyroid hormone also is known to affect nervous system growth and function, it is possible that some of its effects may be mediated through NGF. Using a newly developed, highly sensitive (10-20 pg) radioimmunoassay (RIA) for β-NGF, we studied the effects of thyroxine (T4) and propylthiouracil (PTU) on NGF concentrations in several tissues of the adult male mouse. T4 (25 μg i.p. daily × 12 days) caused a significant increase in submaxillary gland and liver NGF concentrations (180 and 225% respectively) compared to controls (p<0.001), when expressed relative to wet weight or supernatant protein. There was no consistent effect on kidney NGF concentration. PTU (0.05% in drinking water × 21 days) led to a reduction in kidney NGF to 25% of control values (p<0.001) with no discernible effect in sub-maxillary gland and liver NGF concentrations. Conclusions: 1) A highly sensitive RIA for NGF has been developed. 2) T4 appears to have a significant effect on the concentration of NGF in sub-maxillary gland and liver of the adult male mouse, while PTU-induced hypothyroidism affects kidney NGF. These observations in adult mice suggest that thyroid hormone may play an important regulatory role in NGF metabolism.

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

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 recovery day 7. The addition of PTU to normal rat serum in concentrations used during PTU treatment failed to alter Sm activity. The addition of L-triiodothyronine and/or L-thyroxine to hypothyroid serum also did not alter Sm activity. In vitro and in vivo cartilage sulfate incorporation decreased during PTU treatment but it rose to greater than control values during the recovery period. The difference in sulfate incorporation between treated and control rats was maintained throughout the observation periods. The results indicate that incomplete catch-up growth following transient hypothyroidism is the result of factors other than deficient GH or Sm production. The implications of the persistent changes in cartilage sulfate metabolism are not clear, but these findings during recovery suggest the possibility that a disturbance of intrinsic cartilage function is a limiting factor preventing full catch-up growth after PTU-induced hypothyroidism.

Effects of thyroid hormones on the evolution of monoamine oxidase activity in the brain and heart of the developing rat.

The evolution of monoamine oxidase (MAO) activity towards tryptamine has been studied from birth to 20 days post-natal in the brain and heart of male rats. Hyperthyroidism was induced by thyroxine injections and hypothyroidism by PTU administration. The results are expressed per unit of fresh weight and per unit of protein weight. Cardiac MAO is higher in the hyperthyroid animals than in controls as soon as 5 days following birth; the difference between the 2 groups increases until 20 days. The deficiency in thyroid hormones, on the other hand, was followed by a slight decrease in the cardiac enzyme, this decrease reflecting the general deficit in protein synthesis. Brain MAO is not affected by hyperthyroidism, but a clear deficit follows PTU administration. This deficit is significant beginning at 10 days and the difference between the 2 groups increases up to 20 days. The effects of PTU-induced hypothyroidism can be corrected by thyroxine injections. Except for the decrease in the level of cardiac enzyme in hypothyroid animals, all the effects on MAO activity are independent of the total protein content of both organs.