Diphenylhydantoin Stimulates the Intrapituitary Conversion of Thyroxine to Triiodothyronine in the Rat

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Abstract
Treatment of normal rats with diphenylhydantoin (DPH) decreases serum thyroxine (T4) and triiodothyronine (T3) levels without the anticipated rise in serum thyrotropin (TSH). The present work has studied the intrapituitary conversion of T4 to T3 in male Wistar rats, 200-250 g body weight (BW), treated with DPH 5 mg/100 g BW/day for 8 days. A tracer dose of 3’,5’-[125I]T4 (150 µCi) was injected intravenously, and 2 h later hypophyses were removed and homogenized individually at 4 ¤C in ice-cold PBS buffer (pH 7.4). T4 and T3 were extracted in 400 µl n-butanol:2 N HC1 (9:1) and chromatographed in tertiary amyl alcohol:hexane: 1 N ammonia (5:1:6). In 11 untreated control rats, [125I]T3 generated from [125I]T4 deiodination was 35 ± 6% and intact [125I]T4 was 49 ± 9% of total chromatographic radioactivity. In 11 DPH-treated rats [125I]T3 increased (p 125I]T4 decreased (p 4 (2 µg/100 g BW/day for 8 days), DPH similarly increased pituitary 5’-deiodination. Administration of propylthiouracil (PTU) to T4-supplemented rats had no effect on pituitary 5’-deiodination of T4, whereas the addition of DPH to PTU treatment increased [125I]T3 production (p 4 (p 3 (p 4 to T3 may contribute to depress the feedback response of the pituitary gland to low serum thyroid hormone levels.

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