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3,5-Diiodo-L-Thyronine Stimulates Type 1 5'Deiodinase Activity in Rat Anterior Pituitaries in Vivo and in Reaggregate Cultures and GH3 Cells in Vitro¹

Klinische Forschergruppe der Medizinischen Poliklinik der Universität Würzburg (A.B., J.K.), D-97070 Würzburg, Germany; Max-Planck-Institut für Experimentelle Endokrinologie (K.B.), D-30625 Hannover, Germany; and Universitäts-Frauenklinik (H.J.), D-37075 Göttingen, Germany

Address all correspondence and requests for reprints to: J. Köhrle, Medizinische Poliklinik, Röntgenring 11, D-97070 Würzburg, Germany.

Local deiodination of L-thyroxine (T₄) to the active thyroid hormone T₃ via two 5'deiodinase isoenzymes (5'DI and 5'DII) plays an important role for various T₃-dependent functions of the anterior pituitary (AP). Recently, it was reported that 3,5-T2, the 5'deiodination product of T₃, acts as a specific agonist in the feedback mechanism on TSH secretion at the pituitary level. We now examined the effects of 3,5-T2 on pituitary 5'deiodinase activities in vivo in male, adult rats and in vitro using rat AP reaggregate cultures and the somatomammotroph cell line GH3. 5'DI activity in the AP was transiently increased after a single injection of 3,5-T2. Serum TSH levels declined, and 24 h after 3,5-T2 application, ßTSH steady-state mRNA levels in the APs were markedly lower. In reaggregate cultures of the AP, 3,5-T2 stimulated 5'DI activity 24 h after application, dose-dependently. Compared with 5'DI activities, those of 5'DII were an order of magnitude lower, in vivo as well as in vitro, and were rapidly and transiently decreased by the higher dose of 3,5-T2. GH3 cells responded to 3,5-T2 and T₃ by an 1.7-fold stimulation of 5'DI activity. Stimulation of DNA-binding was demonstrated in electrophoretic mobility shift assays for a specific RXR-containing protein complex with a DR+4 thyroid hormone response element of the human type 1 5'DI promoter using nuclear extracts from GH3 cells treated with 3,5-T2. In summary, 3,5-T2 and T₃ exert direct thyromimetic effects on 5'DI activity and TSHß expression at the pituitary level. 5'DI is regulated by its substrate(s) and/or products and may serve an important function within the modulation of thyroid hormone-dependent gene expression in the AP.

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