3,5-diiodo-L-thyronine regulates glucose-6-phosphate dehydrogenase activity in the rats

Thyroid hormones influence the activity of lipogenic enzymes such as malic enzyme (ME) and glucose-6-phosphate dehydrogenase (G6PD). The effect of T-3 on ME is exerted at the transcriptional level, but it is unclear if its effect on G6PD is also nuclear mediated. Furthermore, other iodothyronines that have been shown to posses biological activity (such as diiodothyronines) could contribute to this enzyme's regulation. In this study the effects of 3,5-diiodothyronine (T-2) on the aforementioned enzymes were examined and compared with those of T-3. Rats made hypothyroid by propylthiouracil and iopanoic acid treatment were used throughout. Enzyme activities were determined spectrophotometrically, and G6PD messenger RNA (mRNA) expression was analyzed by Northern blotting using a human G6PD complementary DNA probe. Injections of T-2 to hypothyroid animals significantly enhanced the activity of both enzymes. The effect of T-3 on ME was nuclear mediated and mimicked the effect of T-3. The effects of T-2 and T-3 on G6PD differed. Injection of T-3 into hypothyroid rats induced an increase in both enzyme activity and G6PD mRNA expression, indicating a nuclear-mediated effect. The effect of T-2 on G6PD activity, on the other hand, was not nuclear mediated. The injection of T-2, into hypothyroid animals did not change G6PD mRNA expression, and the strong increase in the enzyme's activity (from 70% to +300%) was unaffected by simultaneous injection of protein synthesis inhibitors. As the lowest dose of 1 mu g T-2/100 g BW affects G6PD activity 3-5 times more than the same dose of T-3, these data provide the first evidence that T-3 is a factor capable of regulating G6PD activity.