TSH secretory responses to prolonged infusion of TRH in hypothyroid rats

Continuous infusion of 0.1-10 micrograms/ml of TRH was performed through chronic i.v. cannulas in unrestrained, unanesthetized hypothyroid rats. Infusion of a constant concentration of TRH induced a peak in the plasma TSH concentration within 5-15 min which declined to the baseline within 1 h. The refractory period lasted 20-40 min after stopping the continuous TRH infusion. A second burst of TSH secretion was induced by increasing the TRH concentration during the refractory period while TRH was being continuously infused. These data indicate that in hypothyroid rats TSH secretion rapidly becomes refractory to continuous exposure to the same concentration of TRH but is stimulated by a higher TRH concentration. This suggests there is heterogeneity in TSH secretory units, which may consist of a constellation of thyrotrophs or of discrete intracellular secretory units, each with a threshold of specific response to TRH.