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Type 2 Iodothyronine Deiodinase in Skeletal Muscle: Effects of Hypothyroidism and Fasting

Department of Endocrinology and Metabolic Diseases (K.A.H., A.A.v.d.K., J.A.R., J.W.S., E.P.C.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands; Department of Endocrinology and Metabolism (M.R.S., E.F., M.J.S.), Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; Center for Human Drug Research (J.B., M.B.v.D.), 2333 CL Leiden, The Netherlands; and Department of Internal Medicine (T.J.V.), Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Karen Heemstra, Leiden University Medical Centre, Department of Endocrinology and Metabolic Diseases, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: k.a.heemstra{at}lumc.nl.

Context: The iodothyronine deiodinases D1, D2, and D3 enable tissue-specific adaptation of thyroid hormone levels in response to various conditions, such as hypothyroidism or fasting. The possible expression of D2 mRNA in skeletal muscle is intriguing because this enzyme could play a role in systemic as well as local T₃ production.

Objective: We determined D2 activity and D2 mRNA expression in human skeletal muscle biopsies under control conditions and during hypothyroidism, fasting, and hyperinsulinemia.

Design: This was a prospective study.

Setting: The study was conducted at a university hospital.

Patients: We studied 11 thyroidectomized patients with differentiated thyroid carcinoma (DTC) on and after 4 wk off T₄ replacement and six healthy lean subjects in the fasting state and during hyperinsulinemia after both 14 and 62 h of fasting.

Mean Outcome Measures: D2 activity and D2 mRNA levels were measured in skeletal muscle samples.

Results: No differences were observed in muscle D2 mRNA levels in DTC patients on and off T₄ replacement therapy. In healthy subjects, muscle D2 mRNA levels were lower after 62 h compared to 14 h of fasting. Insulin increased mRNA expression after 62 h, but not after 14 h of fasting. Skeletal muscle D2 activities were very low and not influenced by hypothyroidism and fasting.

Conclusion: Human skeletal muscle D2 mRNA expression is modulated by fasting and insulin, but not by hypothyroidism. The lack of a clear effect of D2 mRNA modulation on the observed low D2 activities questions the physiological relevance of D2 activity in human skeletal muscle.

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