The concentration of TSH was measured in plasma and anterior pituitary after iv injection of TRH into groups of euthyroid rats. Integration of plasma TSH curves for 120 min after administration of graded doses of TRH (0.05–5.0 μg/100 g BW) showed that a maximal TSH response was achieved with a TRH dose of 1.0 μg/100 g BW or greater. Mean plasma TSH increased to near maximal values at 5 min and to its highest concentration (400–800% increase) 20 min after injection of 5 μg TRH/100 g BW. After 20 min, plasma TSH decreased at a constant fractional rate to pre-TRH injection values, suggesting cessation of TRH-induced TSH secretion after 20 min. Pituitary TSH decreased to a nadir at about 20-30 min after TRH. Moreover, the mean maximal decrement in pituitary TSH (40–45% decrease from control) was equivalent to the amount of TSH metabolized from 0–120 min. The latter was calculated from the mean plasma TSH concentration during this interval and the metabolic clearance rate of TSH. The cessation of TRH effect after about 20 min did not result from negative feedback by T4 or T3. Plasma T4 concentration was unchanged during the period of these observations and plasma T3 increased from 0.49 to 0.89 ng/ml 60 min after TRH injection. The possibility that rapid metabolism of injected TRH limited the duration of the TSH response was tested by injection of a second dose of TRH after the response to the first dose had terminated. In three experiments, the TSH response to the second TRH dose was 24, 25, and 45% of the response to the first TRH dose. The thyrotroph thus appears partially refractory to TRH after initial exposure. Thus, diminished responsivity to TRH may be an additional factor in the regulation of TSH secretion.
ASJC Scopus subject areas