LACK OF EFFECT OF HEXARELIN ON TRH-INDUCED TSH RESPONSE IN NORMAL ADULT MAN

The mechanism of action of the synthetic growth hormone (GH)releasing peptide hexarelin is not yet fully understood. Although a direct effec t on pituitary cells has been demonstrated, the peptide is also active at hypothalamic level, where specific binding sites have been found. The observation that hexarelin acts synergistically with GH-releasing hormone (GHRH) in releasing GH has suggested that it might suppress en dogenous somatostatin secretion. As somatostatin is also inhibitory on TSH secretion, to verify the occurrence of modifications of the somat ostatinergic tone induced by hexarelin, we studied its effects on TRH- induced TSH secretion. Seven normal subjects (4 women and 3 men aged 2 4-29 years) underwent the following tests on 3 different days: a) TRH (200 mu g/l iv)+placebo; b) hexarelin (1 mu g/Kg bw iv) +placebo c) co mbined TRH+hexarelin administration. Hexarelin induced significant and similar increases in serum GH levels when given in combination either with placebo or with TRH (1217+/-470 vs 986+/-208 mu g/min/l p:NS), w hile no modifications of GH levels were seen after TRH+placebo. Serum TSH levels were unmodified by hexarelin+placebo injection. The TSH inc rease elicited by hexarelin+ TRH was superimposable to that elicited b y TRH+placebo (1124+/-530 and 1273+/-380 mU/min/l respectively). Circu lating PRL levels slightly increased after hexarelin+placebo too (897 mu g/min/l), and the PRL response to hexarelin+TRH was slightly, altho ugh not significantly, greater than that observed after TRH+placebo (2 680+/-1517 and 2243+/-1108 mu g/min/l, respectively). In conclusion, o ur data show that hexarelin does not alter basal and TRH-stimulated TS H secretion, thus suggesting that it does not inhibit somatostatin rel ease. Furthermore a modest PRL-releasing effect of this peptide has be en confirmed.