Somatostatin inhibits rat hepatic T4-5'-deiodinase. The effect is independent of the associated hypoinsulinemia.

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RESUMO

Somatostatin decreases the serum 3,5,3'-triiodothyronine (T3) concentration in athyreotic subjects treated with L-thyroxine (T4). The present study was performed to determine the effect of somatostatin on T4-5'-deiodinase activity in rat tissue homogenate preparations. This enzyme is an important regulator of T3 production. Continuous somatostatin infusion at high dose (4 micrograms/kg per min subcutaneously) and low dose (0.8 micrograms/kg per min subcutaneously) for 48-72 h significantly increased (P less than 0.001) the mean aorta plasma somatostatin-like immunoreactivity concentration to 786 +/- 65 and 448 +/- 58 pg/ml, respectively compared with the normal mean of 69 +/- 17 pg/ml in the carbohydrate-fed rat (20% glucose in water ad lib.). The mean hepatic T4-5'-deiodinase activity at both 48 h (100 +/- 5 pmol/min per 100 mg protein) and 72 h (90 +/- 7 pmol/min per 100 mg protein) was significantly reduced in the high-dose group (P less than 0.005), compared with the mean enzyme activity in the glucose-fed control group (138 +/- 6 pmol/min per 100 mg protein). There was a negative correlation (r = -0.9, P less than 0.01) between the alterations in the peripheral plasma somatostatin-like immunoreactivity concentration and hepatic T4-5'-deiodinase activity. High-dose somatostatin did not consistently lower the serum T3 concentration in the glucose-fed rat. Somatostatin had no effect on pituitary T4-5'-deiodinase activity in the glucose-fed rat. High-dose somatostatin also significantly inhibited (P less than 0.01) the glucose-refeeding reactivation of hepatic T4-5'-deiodinase in the 72-h-fasted rat. The mean enzyme activity after 96 h was 96 +/- 8 pmol/min per 100 mg protein compared with 127 +/- 4 pmol/min per 100 mg protein in the refed control group. Somatostatin had a similar inhibitory effect on serum T3. There was a positive correlation (r = 0.5, P less than 0.01) between the somatostatin-induced alterations in serum T3 and hepatic T4-5'-deiodinase during refeeding. A significant positive correlation (r = 07, P less than 0.005) was noted between the somatostatin effect on hepatic T4-5'-deiodinase activity and the induced hypoinsulinemia in the fed group. In addition, a significant negative correlation (r = -0.9, P less than 0.001) was noted between the suppressed enzyme activity and the serum glucose/insulin ratio in the refed group. However, although low-dose somatostatin also induced the same degree of hypoinsulinemia (P less than 0.05) in the fed and refed groups it had no effect on hepatic T4-5'-deiodinase activity. Furthermore, despite the induction of hyperinsulinemia during refeeding, the high dose somatostatin inhibitory effect on enzyme activity persisted. Thus, somatostatin inhibited hepatic T4-5'-deiodinase activity in the carbohydrate-fed rat and prevented the carbohydrate-refeeding normalization of enzyme activity in the 72-h-fasted rat. The effect of somatostatin on enzyme activity was independent of the associated hypoinsulinemia. In the carbohydrate-fed animal the somatostatin effect was selective, as the hormone had no effect on pituitary T4-5'-deiodinase activity. These data suggest that somatostatin could play a role in the peripheral metabolism of thyroid hormones.

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