Autoregulatory Control of Thyrotropin in Rabbits

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Abstract
Studies were designed to determine whether an autoregulation system exists for TSH in the rabbit. For this purpose, a species-specific radioimmunoassay for rabbit TSH that does not cross-react with human (h) TSH was developed. Hypothyroid animals were studied at varying time periods up to 3 mo. after either surgical thyroidectomy or propylthiouracil (PTU) treatment. Highly purified hTSH was injected i.v. at doses of 0 (saline control), 0.1, 0.3, 1, 3 and 10 .mu.g into unanesthetized rabbits bearing chronically implanted Silastic catheters. Blood samples were obtained at -30, 0, 10, 20, 30, 60, 120, 180, 240, and 300 min and 24 h. Doses between 0.3 and 10 .mu.g hTSH produced a prompt fall (10 min) in rabbit TSH in hypothyroid rabbits studied 8-21 days after thyroidectomy. The minimum dose of hTSH that significantly suppressed rabbit TSH was 0.3 .mu.g. This dose produced a peak value of hTSH in rabbit serum of 1.3 .+-. 0.1 (.+-. standard error of the mean) ng/ml 10 min after injection, which translates into a bioassay potency of 2.0 .mu.U/ml (close to the physiological level in humans). A dose-response relationship existed between the hTSH dose injected and the duration and magnitude of suppression of rabbit TSH. This response to TSH was specific; 10 .mu.g hTSH produced no change in endogenous rabbit serum LH [luteinizing hormone] and, conversely, 10 IU hLH produced no change in rabbit serum TSH. In contrast to these striking effects in acute hypothyroid animals, hTSH produced no detectable suppression of rabbit TSH in animals that were hypothyroid for 2-3 mo. The sensitivity of the autoregulatory system to the suppressive effects of exogenous hTSH decreased with increasing duration of hypothyroidism; a time-response relationship existed. A sensitive and specific autoregulatory control system for TSH exists in the rabbit; and as the duration of hypothyroidism increases, the sensitivity of the autoregulatory system to the suppressive effects of endogenous TSH changes.

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