Thyrotropin Response to Repeated Injection of Thyrotropin Releasing Hormone

Abstract

The effect of repeated TRH injection on TSH secretion was examined both in human and rat. In 5 healthy men and 4 hypothyroidal subjects, 500 µg of TRH was injected subcutaneously every 12 hours for 3 doses. In both groups, plasma TSH responses as well as the basal levels were lower in the third injection than in the first. Plasma T3 and T4 increased significantly in healthy subjects, but not in hypothyroids. In Wistar strain male rats, 50 µg of TRH was injected intraperitoneally every 12 hours 4 times, and 4, 8, and 12 hours after the last injection, TSH response in vivo and in vitro to newly administered TRH was measured. Four and 8 hours after the last injection, TSH response was suppressed. Serum T3 and T4 were elevated at 4-hour point, but was decreased at 8-hour point. Even in thyrodectomized rats, the response of TSH to TRH in vivo and in vitro was suppressed 8 hour after the last serial injection without any change of T3 or T4. The pituitary content of TSH was decreased 8 hours after the injection. The TSH response to TRH in vivo and in vitro had recovered by 12 hours after the last injection. These results demonstrate that repeated injections of large doses of TRH cause a transient deficiency of pituitary releasable pool of TSH, resulting an attenuated response in blood TSH.