EFFECT OF CORTISONE ON THE ACTION OF THYROXINE AND TRIIODOTHYRONINE IN HYPOPHYSECTOMIZED RATS¹,²

Abstract

The effect of cortisone has been observed on the oxygen consumption of hypophysectomized rats given thyroxine and triiodothyronine. Similarly, the effect of cortisone has been observed on the disappearance of P 32 from P 32 -labeled red cells injected into hypophysectomized rats receiving thyroxine and triiodothyronine.Cortisone inhibited the effect of thyroxine both on oxygen consumption and P 32 disappearance but failed to inhibit the stimulating effect of triiodothyronine.The results are consistent with the hypothesis that cortisone inhibits the peripheral degradation of thyroxine to triiodothyronine.LTHOUGH an inhibiting effect of cortisone on thyroid function has been demonstrated in many clinical and experimental studies, the precise mechanism of this action is not known. Suggestions have included a depressive action on the pituitary gland (1), on the thyroid (2, 3, 4), an increased renal disposal of iodide (5), and a direct antagonistic effect on the circulating hormone (6, 7).It is also possible that cortisone interferes with the normal degradation of thyroxine. Gross and Leblond (8) found that radioactive triiodothyronine (T3) appeared in the plasma after injection of labeled thyroxine (T4) into thyroidectomized rats. Similar observations have been made in myxoedematous patients (9). These experiments and in vitro observations of Larson et al. (10) indicate the existence of extra-thyroidal dehalogenation of thyroxine. Others have suggested that deiodination of thyroxine to triiodothyronine is a step essential to metabolic effect and that a partially deiodinated product is the active form of the thyroid hormone (11,12,13,14).The present experiments were designed to test the hypothesis that the anti-thyroid effect of cortisone is due to peripheral inhibition of the degra-

Physiological Mammalogy

“…Adrenalectomy inhibits the release of iodine and therefore of thyroid hormone from the thyroid glands of rats (Fllickiger and Verzar, 1955). Bastenie and Ermans (1958) have shown that cortisone, in addition to its effect on the secretion of TSH, inhibits the stimulating effect of thyroxine on oxygen consumption and phosphorus turnover but fails to inhibit these actions of triiodothyronine. These authors concluded that cortisone inhibits the peripheral degradation of thyroxine to triiodothyronine.…”