The vagus nerve as a regulator of growth hormone secretion

The growth hormone (GH) axis is mainly regulated by the growth hormone releasing hormone (GHRH) and somatostatin (SS) hypothalamic peptides. Nevertheless, since ghrelin peptide was discovered as the natural ligand for growth hormone secretagogue receptor (GHS-R), the mechanism of GH regulation has acquired a new dimension. It was described that ghrelin possesses a relevant effect inducing GH secretion when it is administered peripherally. A role of the vagus nerve mediating ghrelin action has been described although this effect is not understood. Under this context the main objective of this work was to determine the possible involvement of the vagus in the somatotroph axis regulation. The results in this manuscript show that animals with a disruption of the vagus connection presented lower basal IGF-1 and GH levels, a decreased GH response to peripheral GHRH administration and a marked diminution in the GH response to peripheral and central ghrelin treatments. In addition, vagotomized animals showed a down-regulation of GHRH mRNA in the arcuate nucleus of the hypothalamus and a down-regulation in both GHRH and GHS receptors' mRNA at the pituitary level. In conclusion, the present work reveals that the vagus nerve is crucial in growth hormone regulation and essential for the full GH-releasing effect of ghrelin.

Research Highlights
► The disruption of the peripheral–central communication through the vagus by surgical vagotomy induces a decrease in the GH basal levels in rat.
► The vagus nerve was found to be involved in the normal pattern of GHRH expression in the hypothalamus.
► The vagus nerve acts at the pituitary level regulating GHS-R and GHRH-R expressions.