-Using a continuous subcutaneous octreotide infusion to create constant supraphysiological somatostatinergic tone, we have previously shown that growth hormone (GH) pulse generation in women is independent of endogenous somatostatin (SRIH) declines. Generalization of these results to men is problematic, because GH regulation is sexually dimorphic. We have therefore studied nine healthy young men (age 26 Ϯ 6 yr, body mass index 23.3 Ϯ 1.2 kg/m 2 ) during normal saline and octreotide infusion (8.4 g/h) that provided stable plasma octreotide levels (764.5 Ϯ 11.6 pg/ml). GH was measured in blood samples obtained every 10 min for 24 h. Octreotide suppressed 24-h mean GH by 52 Ϯ 13% (P ϭ 0.016), GH pulse amplitude by 47 Ϯ 12% (P ϭ 0.012), and trough GH by 39 Ϯ 12% (P ϭ 0.030), whereas GH pulse frequency and the diurnal rhythm of GH secretion remained essentially unchanged. The response of GH to GH-releasing hormone (GHRH) was suppressed by 38 Ϯ 15% (P ϭ 0.012), but the GH response to GH-releasing peptide-2 was unaffected. We conclude that, in men as in women, declines in hypothalamic SRIH secretion are not required for pulse generation and are not the cause of the nocturnal augmentation of GH secretion. We propose that GH pulses are driven primarily by GHRH, whereas ghrelin might be responsible for the diurnal rhythm of GH.somatotropin; pulsatility; diurnal rhythm; octreotide; ghrelin; somatotropin-releasing hormone THE MAINTENANCE of pulsatile and diurnal growth hormone (GH) secretion is controlled by several factors, including hypothalamic GH-releasing hormone (GHRH) and somatostatin (SRIH). In addition, the recently discovered gastric peptide ghrelin may play a role. The relative role of each of these factors in coordinating pulsatile GH secretion is not clear. (11).In vitro and in vivo studies in animals have shown that SRIH withdrawal reliably results in rebound GH release, suggesting decline in endogenous SRIH secretion as the driving force of GH pulses (4,20,26,36,38). In rats of both sexes, hypothalamic GHRH is critically important for GH pulse generation (31, 37), but the role of SRIH in the regulation of GH pulsatility is clearly sexually dimorphic. In male rats, SRIH appears to be secreted episodically and to play an important role in the regulation of GH pulsatility (31, 37). In contrast, in female rats, SRIH appears to be secreted in a more continuous fashion and is unlikely to be important in the generation of GH pulses (30). In other species such as sheep, hypothalamic GHRH appears to be primarily responsible for the generation of GH pulses (8,23,39,41).In humans, endogenous GHRH is required for GH pulsatility (29). However, it is not clear whether periodic hypothalamic GHRH release is responsible for the initiation of GH pulses or whether GHRH is required for the action of other factors. Previous studies in healthy young men showed persistence of GH pulses during continuous intravenous GHRH infusions, suggesting that periodic declines of the somatostatinergic tone were responsible for the initiation of...