Hypothalamic Somatostatin Mediates the Suppression of Growth Hormone Secretion by Centrally Administered Thyrotropin-Releasing Hormone in Conscious Rats*

Abstract

The effect and mechanism of action of central TRH on the regulation of GH [growth hormone] secretion was studied in conscious male rats with indwelling intraatrial and intracerebroventricular (icv) cannulae. Plasma GH was measured every 10-20 min from 1000-1400 h by repeated blood sampling. In animals that received saline i.v. or icv, GH secretion was pulsatile, with peak hormone levels occurring at 1120-1200 h. TRH (10 .mu.g), injected icv at 1100 h, inhibited spontaneous GH secretion, and mean plasma GH levels remained suppresed (< 20 ng/ml) for at least 3 h after injection. In contrast, an i.v. injection of the same dose of TRH at 1100 h did not significantly affect spontaneous GH secretion. I.v. injection of human GH-releasing factor [1-40] (hGRF, 1 .mu.g) at 1100 h in animals injected 5 min earlier with saline (10 .mu.l, 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 .mu.g) 5 min before the i.v. injection of hGRF exhibited an attenuated GH response to hGRF (peak values, 115 .+-. 28 ng/ml; P < 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, i.v.) but not with normal serum (P < 0.001). An inhibitory role in central TRH is evident in the regulation of spontaneous GH secretion in the rat that is mediated by stimulation of hypothalamic somatostatin.