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3,5-Diiodo-L-Thyronine Regulates Glucose-6-Phosphate Dehydrogenase Activity in the Rat¹

Dipartimento di Fisiologia Generale ed Ambientale, Università di Napoli Federico II (A.Lo., L.B., S.D., F.G.), and Istituto Internazionale di Genetica e Biofisica (M.V.U.), 80134 Naples; and Facoltà di Scienze, Università degli Studi del Sannio Benevento (M.M., V.C.), 82100 Benevento; and Dipartimento di Scienze della Vita, Seconda Università degli Studi di Napoli (A.La.), 81100 Caserta, Italy; and Department of Obstetric and Gynecology, Yale University School of Medicine (S.D.), New Haven, Connecticut 06520

Address all correspondence and requests for reprints to: Dr. F. Goglia, Dipartimento di Fisiologia Generale ed Ambientale, Università di Napoli Federico II, Via Mezzocannone 8, 80134 Naples, Italy. E-mail: goglia{at}biol.dgbm.unina.it

Thyroid hormones influence the activity of lipogenic enzymes such as malic enzyme (ME) and glucose-6-phosphate dehydrogenase (G6PD). The effect of T₃ 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 (T₂) on the aforementioned enzymes were examined and compared with those of T₃. 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 T₂ to hypothyroid animals significantly enhanced the activity of both enzymes. The effect of T₂ on ME was nuclear mediated and mimicked the effect of T₃. The effects of T₂ and T₃ on G6PD differed. Injection of T₃ into hypothyroid rats induced an increase in both enzyme activity and G6PD mRNA expression, indicating a nuclear-mediated effect. The effect of T₂ on G6PD activity, on the other hand, was not nuclear mediated. The injection of T₂ 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 µg T₂/100 g BW affects G6PD activity 3–5 times more than the same dose of T₃, these data provide the first evidence that T₂ is a factor capable of regulating G6PD activity.

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