ABSTRACT

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 μCi [¹²⁵I]T₄ or [¹²⁵I]T₃ were added. After incubation for 2 h at 37 °C, radioactive compounds were identified by paper chromatography. Both AMD and IA given in vivo blocked T₄ to T₃ conversion significantly (P<0·005). When added in vitro, AMD failed to inhibit T₄ deiodination to T₃ whereas IA induced a significant (P<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< 0·001) and decrease in T₃ (P< 0·001) did occur after AMD or IA treatment, plasma TSH in AMD-treated rats was decreased (P<0·001), while in IA-treated animals it was increased (P< 0·001), thus indicating that AMD did not inhibit pituitary type-II 5′-monodeiodinase.

In summary, these data suggest that the hypometabolism induced by AMD in rat myocardium through a decrease in the supply of T₃ is not responsible for the anti-arrhythmic activity of this drug since IA, which is not an anti-arrhythmic compound, elicited the same effect on cardiac T₃. It follows that inhibition of 5′-deiodinase and the anti-arrhythmic activity of AMD are independent properties.

Journal of Endocrinology (1989) 121, 431–434

ABSTRACT

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 I. Seven days after ovariectomy, animals were separated into five groups: I, euthyroid controls; II, hypothyroid controls; III, hypothyroid and injected with oestradiol benzoate (10 μg/day for 10 days); IV, hypothyroid and injected with T₄ (4 μg/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 <0·01) and 12·7 ± 1·7 fmol/mg DNA (P <0·01 compared with group I). In group III, cytosolic receptor concentrations decreased when compared with those in group II (P <0·05), whereas nuclear receptor concentrations rose significantly (P <0·01). Group IV had both pituitary cytosolic and nuclear receptors increased (P <0·01 compared with group II). In group V there were no changes in cytosolic receptor concentrations but a significant (P <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 <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 <0·05). Neither hormone caused changes in nuclei. The results show that there is a pronounced decrease in pituitary and hypothalamic (nuclei) oestrogen receptors in untreated hypothyroid rats and that this decrease can be reversed by T₄ treatment.

J. Endocr. (1988) 119, 383–387