SOMATOSTATIN WITHDRAWAL ALONE IS AN INEFFECTIVE GENERATOR OF PULSATILE GROWTH-HORMONE RELEASE IN MAN

To assess the relative roles of growth hormone-releasing hormone (GHRH) pulse and somatostatin withdrawal as potential generators of pulsatile growth hormone (GH) release in humans, we studied GH responses to iv bolus GHRH (1 mug/kg) and to termination of a 4 h iv somatostatin infusion (7.2 mug.kg-1.h-1) in five normal young men, and in five men with previously diagnosed isolated GH deficiency. The patients were diagnosed 8-15 years previously on the basis of typical auxological and hormonal criteria, were treated with exogenous GH and were off GH therapy for 1.5-8.9 years prior to this study, Growth hormone rises to a bolus GHRH were similar between the controls and the patients (maximum GH 27.3 +/- 15.3 vs 8.0 +/- 4.0 mug/l). The controls exhibited only a small GH rise to somatostatin withdrawal (maximum GH 2.9 +/- 1.2 mug/l), while the patients did not (maximum GH 0.7 +/- 0.1 mug/l: p < 0.05). We conclude that somatostatin withdrawal by itself is an ineffective promoter of GH pulsatility. Periodic quiescence of somatostatinergic neurons must be associated with a concomitant GHRH pulse in order to result in a robust GH pulse.