Context: The mechanisms underlying the well known glucagon-induced satiety effect are unclear. Recently we could show that glucagon induces a remarkable decrease in the orexigenic hormone ghrelin that might be responsible for this effect.

Objective: To evaluate the putative role of the hypothalamic pituitary axis in the glucagon's suppressive effect on ghrelin secretion.

Design, subjects and methods: Prospectively, we studied the endocrine and metabolic responses to intramuscular glucagon administration in 22 patients (16 males; age 21-68 yr; BMI 28.1 ± 1.1 kg/m²) with a known hypothalamic-pituitary lesion and at least one pituitary hormone deficiency. Control experiments were performed in 27 healthy subjects (15 males; age 19-65 yr; BMI 25.5 ± 0.9 kg/m²).

Results: The suppression of ghrelin by glucagon measured as AUC₂₄₀min was significantly greater in controls when compared with patients (P < 0.01). While there was a significant decrease in ghrelin in controls (P < 0.001), ghrelin was almost unchanged in patients (P = 0.359). Changes in glucagon, glucose and insulin levels were comparable between both groups.

Conclusions: We show that the hypothalamic-pituitary axis plays an essential role in the suppression of ghrelin induced by i.m. glucagon administration. Glucagon significantly decreases ghrelin levels in healthy subjects. However, in the absence of an intact hypothalamic-pituitary axis this effect was abolished. The mechanisms responsible for our observation unlikely include changes in glucose or insulin levels.