The effect and mechanism of action of central TRH on the regulation of GH secretion was studied in conscious male rats with indwelling intraatrial and intracerebroventricular (icv) cannulae. Plasma GH was measured every 10-20 min from 1000 h-1400 h by repeated blood sampling. In animals that received saline iv or icv, GH secretion was pulsatile, with peak hormone levels occurring at 1120-1200 h. TRH (10 micrograms), injected icv at 1100 h, inhibited spontaneous GH secretion, and mean plasma GH levels remained suppressed (less than 20 ng/ml) for at least 3 h after injection. In contrast, an iv injection of the same dose of TRH at 1100 h did not significantly affect spontaneous GH secretion. Intravenous injection of human GH-releasing factor [1-40] (hGRF, 1 micrograms) at 1100 h in animals injected 5 min earlier with saline (10 microliters, icv) stimulated GH release, with peak values (748 +/- 63 ng/ml, mean +/- SE) observed 10 min after injection. However, animals injected icv with TRH (10 micrograms) 5 min before the iv injection of hGRF exhibited an attenuated GH response to hGRF (peak values, 115 +/- 28 ng/ml; P less than 0.001 vs. saline icv + hGRF). The inhibition of GH secretion by central TRH was abolished by pretreatment of animals with antisomatostatin serum (0.5 ml, iv) but not with normal serum (P less than 0.001). These results suggest an inhibitory role of central TRH in the regulation of spontaneous GH secretion in the rat that is mediated by stimulation of hypothalamic somatostatin.