The suggestion has been made that the substantial increases in pituitary thyrotrophin (TSH) concentration reported in hypothyroid rats by some workers might be attributable to incomplete surgical thyroidectomy or partial goitrogen block. An attempt, therefore, was made to correlate the severity of hypothyroidism with the storage and release rate of TSH. Female and male Long-Evans rats were made hypothyroid either by surgical thyroidectomy or by administration of propylthiouracil (PTU). Rats were also surgically or chemically thyroidectomized and injected daily with subnormal doses of thyroxine (T4) so as to ameliorate the hypothyroidism. Pituitary and serum levels of TSH were quantified, both by bioassay (stasis tadpole), and radioimmunoassay. The results showed TSH reduced in the pituitary of the severely hypothyroid rat. In both females and males, amelioration of the hypothyroidism with small chronic doses of T4 did not increase bioassayable or immunoassayable TSH stores. Paradoxially, bioassay showed serum TSH titers increased in females inversely proportional to the apparent severity of the hypothyroidism. However, radioimmunoassay of the sera of males, whose hypothyroidism was ameliorated by T4, revealed no significant increases in TSH over thyroidectomy controls. Therefore, the results were unclear as to whether subnormal quantities of T4 increase TSH release from the pituitary. The differences in serum TSH concentration between hypothyroid-ameliorated females and males are not attributable to sex or to differences in the reliability between the bioassay and immunoassay. However, bioassayable increases in TSH stores may perhaps reflect an influence exerted by pituitary gonadotrophins or sex steroids.
The efficacy of iodide and thyroxine in ameliorating the several deficiencies occasioned by thyroidectomy in male and female rats was compared in order to obtain indirect evidence for extrathyroidal thyroxine formation. More direct refutation of the opposing concept that iodide simulates the action of thyroxine was also sought in experiments with propylthiouracil (PTU) and tribromothyronine. In all indices of thyroxine action examined in thyroidectomized rats, namely, growth, metabolic rate, heart rate, and pituitary, adrenal and reproductive function, the restorative or maintenance activities of large quantities of iodide were identical with those of minute quantities of thyroxine. Effective doses of iodide presumably resulted in the formation of thyroxine in quantities equivalent to the daily injection of 0.25-0.5 ng. PTU abolished most of the growth response to iodide, while not interfering with the action of thyroxine, which pro
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