Some Influences of Thyroid on the Pituitary-Adrenal Axis

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Abstract
The influence of thyroid hormones on the pituitary-adrenal axis in rats was investigated using the following parameters: 1) plasma corticosteroid levels; 2) production of A4-3-ketosteroids by adrenal fragments in vitro; 3) pituitary ACTH content; 4) volume of distribution of injected corticosterone; 5) adrenal weight. Mild hyper thy roidism was induced by adding thyroglobulin to the diet. Hypothyroidism was induced by goitrogen administration, by thyroidectomy, or by hypophysectomy to permit segregation of extrahypophysial and extrathyroidal effects. Hyperthyroidism induced an increase in adrenal weight, which could be prevented by injection of prednisolone tertiarybutylacetate or by hypophysectomy. Plasma corticosteroid levels were significantly higher in thyroid-treated animals (intact or thyroidectomized) than in controls, following ACTH injection. However, this increase was attributable to a 50% reduction in the volume of distribution of corticosterone in thyroidtreated animals. Adrenals of hyperthyroid rats were similar to those of normal rats in production of A4-3-ketosteroids in vitro. When hypothyroidism was induced by means of thiouracil in the diet, plasma corticosteroid response to ACTH injection was depressed, whereas adrenal response to ACTH in vitro was enhanced, if anything,’ despite adrenal atrophy. When hypothyroidism was induced by thyroidectomy, adrenal corticoidogenesis in vitro was slightly depressed, but plasma corticosteroid response to ACTH injection was adequate. The effects of hypothyroidism on the adrenal were markedly different from those of prednisolone blockade, in which adrenal response to ACTH in vivo or in vitro was markedly reduced. Rats which were made hypothyroid by hypophysectomy and maintained on constant small doses of ACTH likewise showed an adequate rise in plasma corticosteroids in response to a test dose of ACTH. Thyroid treatment of hypophysectomized rats did not influence the parameters under investigation, unless daily ACTH maintenance doses had also been provided. Thyroid significantly depressed adrenal corticoid production in vitro in ACTH-maintained hypophysectomized rats and effected a decrease in volume of distribution of corticosterone in vivo.