The present work studied the effects of amiodarone (AMD) and iopanoic acid (IA) on the conversion of thyroxine (T4) to tri-iodothyronine (T3) by rat myocardium. In vivo: male Wistar rats weighing 200-250 g were injected i.p. with AMD (2.5 mg/100 g body weight per day for 12 days) or IA (5 mg/100 g body weight every 12 h for 72 h). Hearts were then removed and processed as in the in-vitro studies. In vitro: hearts were homogenized in Krebs-Ringer phosphate buffer (pH 7.4) and AMD (0.1 mmol/l) or IA (10 mmol/l) plus dithiothreitol (8 mmol/l) and 0.01 microCi [125I]T4 or [125I]T3 were added. After incubation for 2 h at 37 degrees C, radioactive compounds were identified by paper chromatography. Both AMD and IA given in vivo blocked T4 and T3 conversion significantly (P less than 0.005). When added in vitro, AMD failed to inhibit T4 deiodination to T3 whereas IA induced a significant (P less than 0.005) decrease in T3 generation. Deiodination of [125I]T3 by heart homogenates was not altered by AMD or IA. While the expected increase in circulating T4 (P less than 0.001) and decrease in T3 (P less than 0.001) did occur after AMD or IA treatment, plasma TSH in AMD-treated rats was decreased (P less than 0.001), while in IA-treated animals it was increased (P less than 0.001), thus indicating that AMD did not inhibit pituitary type-II 5'-monodeiodinase.(ABSTRACT TRUNCATED AT 250 WORDS)
To examine the role of thyroid parasympathetic innervation in organ's function, rats subjected to inferior laryngeal nerve (ILN) section were employed. This procedure decreased thyroid [3H]choline uptake by about half. Bilaterally ILN-sectioned rats treated with methylmercaptoimidazole for 4 days exhibited a significant impairment of the methylmercaptoimidazole-induced goitrogenic response. Unilateral ILN section resulted in further atrophy of the ipsilateral thyroid lobe in hypophysectomized rats. One week after ILN section a significant decrease of serum T4 and an increase of serum TSH were observed. Bilateral ILN section generally decreased circulating T4 for up to 28 days after surgery, while a unilateral ILN section caused a transient T4 decrease for 1 week after surgery. Compensatory thyroid growth in rats subjected to unilateral thyroidectomy (hemi Tx) and ILN section performed ipsilaterally to the remaining lobe, was significantly smaller than that of rats subjected to hemi Tx alone. Hemi Tx depressed serum T4 and increased serum TSH levels significantly. These hormonal changes were prevented by unilateral superior cervical ganglionectomy (SCGx), but were unaffected by ILN section. The combination of SCGx and ILN section negated the facilitating effect of SCGx on thyroid secretion and impaired the increase in compensatory thyroid growth brought about by thyroid sympathetic denervation. Thyroid mitotic index studies in hemi Tx rats receiving ILN section, SCGx, or a combination of both indicated that the increase in the number of follicular mitosis caused by hemi Tx was significantly impaired by ILN section and was significantly increased by SCGx. SCGx potentiation of thyroid follicular mitotic activity was partially prevented by concomitant ILN section. These results support a significant role of thyroid sympathetic and parasympathetic innervation in the control of organ's growth and secretory activity.
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 < 0.001) and [125I]T4 decreased (p < 0.02). The DPH effect was blocked in rats treated for 2 days with iopanoic acid 10 mg/100 g BW, though blocking was not seen in rats treated with half the dose of iopanoic acid. In normal rats receiving supplemental doses of T4 (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 < 0.01). Serum T4 (p < 0.001) and T3 (p < 0.01) were decreased after DPH therapy, while serum and pituitary TSH were not altered. The DPH-stimulated deiodination of T4 to T3 may contribute to depress the feedback response of the pituitary gland to low serum thyroid hormone levels.
The effects of thyroxine (T4) were studied on the concentration of oestrogen receptors in the anterior pituitary gland and hypothalamus of ovariectomized euthyroid and hypothyroid rats. A group of rats was made hypothyroid by the administration of 131I. Seven days after ovariectomy, animals were separated into five groups: I, euthyroid controls; II, hypothyroid controls; III, hypothyroid and injected with oestradiol benzoate (10 micrograms/day for 10 days); IV, hypothyroid and injected with T4 (4 micrograms/day for 10 days) and V, hypothyroid and injected with both oestradiol and T4 as described above. In group I, oestrogen receptor levels in pituitary cytosol were 44.4 +/- 3.4 (S.D.) fmol/mg protein and in the nucleus 47.7 +/- 4.0 fmol/mg DNA. In group II the respective values were 12.8 +/- 1.7 fmol/mg protein (P less than 0.01) and 12.7 +/- 1.7 fmol/mg DNA (P less than 0.01 compared with group I). In group III, cytosolic receptor concentrations decreased when compared with those in group II (P less than 0.05), whereas nuclear receptor concentrations rose significantly (P less than 0.01). Group IV had both pituitary cytosolic and nuclear receptors increased (P less than 0.01 compared with group II). In group V there were no changes in cytosolic receptor concentrations but a significant (P less than 0.01) rise in nuclear receptors as compared with group II. Hypothalamic oestrogen receptors in untreated hypothyroid rats (group II) were unchanged in the cytosol and diminished (P less than 0.01) in the nucleus in relation to euthyroid controls (group I). Thyroxine, but not oestrogen, was effective in increasing the concentration of cytosolic receptors (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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