Differential somatostatin sensitivity of corticotropic and somatotropic responses following amino acid infusion.

objectiveAmino acids stimulate pituitary hormone secretion, but whether somatostatin-sensitive pathways differentially regulate activation of the corticotropic and somatotropic axes during amino acid infusion remains unclear. We investigated whether somatostatin signalling constrains growth hormone secretion following amino acid infusion differently from ACTH and cortisol responses in humans.

methodsWe conducted a randomized, within-subject crossover study in 15 healthy adults with three morning visits: amino acid infusion plus saline, somatostatin analogue infusion plus saline, and combined amino acid plus somatostatin analogue infusion. Vamin, an amino acid mixture, was infused at 331 mg·kg-1·h-1 from 0 to 45 min, and octreotide, a somatostatin analogue, was infused at 200 ng·kg-1·min-1 from -75 to 165 min; blood was sampled from -75 to 300 min. Post hoc exploratory outcomes included baseline-subtracted area-under-the-curve measures for cortisol, ACTH, and growth hormone, analysed using repeated-measures mixed-effects models.

resultsFollowing amino acid infusion, ACTH and cortisol showed rapid responses, peaking around 45 min, whereas growth hormone increased gradually and peaked around 120 min. Compared with somatostatin analogue alone, amino acid infusion increased peak concentrations and baseline-subtracted exposures for cortisol, ACTH, and growth hormone. Co-infusion with somatostatin analogue substantially reduced ACTH and cortisol responses but almost completely abolished growth hormone secretion.

conclusionCorticotropic and somatotropic responses were observed following intravenous amino acid infusion in humans, with markedly different somatostatin sensitivity. Growth hormone secretion was almost completely suppressed by somatostatin analogue administration, whereas ACTH and cortisol responses remained partly preserved, suggesting that HPA axis activation can partly escape somatostatin inhibition. SIGNIFICANCE STATEMENT: Amino acids are commonly viewed as nutritional substrates, but they can also act as endocrine stimuli. In this study, intravenous amino acid infusion was followed by activation of both the corticotropic and somatotropic axes in healthy adults, producing rapid ACTH-cortisol responses and a delayed growth hormone response. The findings show that these responses differ markedly in their sensitivity to somatostatin signalling: growth hormone secretion was almost completely suppressed by somatostatin analogue administration, whereas ACTH and cortisol responses remained partly preserved. These findings provide physiological insights into how corticotropic and somatotropic responses following amino acid infusion differ in their sensitivity to octreotide.