Clonidine pretreatment modifies the growth hormone secretory pattern induced by shortterm continuous GRF infusion in normal man

Abstract

The aim of this study was to investigate the effect of a single dose of clonidine on the pattern of GH release in response to a 10-hour continuous GRF infusion in normal man. Plasma GH was analysed in samples withdrawn at 20-minute intervals, from 0900 to 1900 h, according to the following protocols: in a control study, a placebo was given at 1000 h; in other experiments, clonidine (300 micrograms, orally) was given at 1000 h, alone or together with a continuous intravenous infusion of GRF 1-29 (0.3 micrograms/kg/h) starting at this time. In another experiment, the continuous infusion of GRF 1-29 was preceded by placebo administration at 1000 h. Eight normal volunteers (four women and four men), aged 19-24 years were studied. Plasma GH levels were measured by RIA. Analysis of the pattern of GH secretion was performed using cluster analysis. Clonidine induced a slight but significant increase in plasma GH values, peaking 60 to 120 minutes later; however, no significant changes were observed in indices of total and pulsatile GH release for the whole sampling period in this study. Continuous GRF administration led to increased episodic GH secretion, by augmenting GH peak amplitude, although peak frequency was not modified. An increase in interpulse GH values was also observed during GRF infusion. Pretreatment with clonidine clearly changed the pattern of GH release during GRF infusion: the amount of GH secreted was significantly higher, the number of GH peaks significantly increased, and almost all the GH was secreted within them. These data concord with our previous demonstration that clonidine disrupts the hypothalamic-somatotroph rhythm by inhibiting the hypothalamic release of somatostatin. Given that clonidine pretreatment induced a more physiological episodic pattern of GRF-induced GH release, the possibility of combining clonidine and GRF therapy for short stature in children is envisaged.