We have recently explored the involvement of ghrelin in the eating response to stress in humans and found that ghrelin levels increased in parallel to cortisol after a standardized psychological stress. To further elucidate this interaction, we examined the ghrelin response to pharmacological manipulation of the HPA axis.
Following approval from the local Ethical Committee, six lean, healthy male volunteers were examined on two occasions. Blood samples were collected every 30 min for two sequential periods of 2 h. Initially, a baseline period was followed by i.v. injection of ACTH 250 μg. Subsequently, metyrapone (23 g) was administered at midnight and in the following morning the initial 2-h sampling was followed by i.v. injection of hydrocortisone 100 mg.
Mean total ghrelin levels during the 2-h period after metyrapone administration was significantly lower than during the period following ACTH administration (P=0.033). After ACTH stimulation, there was a positive correlation between total ghrelin and cortisol AUC (r=0.876; P=0.021). Mean acylated ghrelin levels were lower during the post metyrapone sampling than in the baseline period (P=0.058). Furthermore, acylated ghrelin levels significantly increased after acute hydrocortisone administration (P=0.032) and was positively correlated with the decrease in ACTH (r=0.825; P=0.043) and the increase in cortisol (r=0.86, P=0.06). There was a highly positive correlation between total and acylated ghrelin levels during all phases of the study (r=0.96, P=0.002).
In conclusion, increased cortisol levels secondary to ACTH stimulation or hydrocortisone administration is associated with increments in plasma ghrelin levels, whereas central stimulation of the HPA axis by blocking cortisol synthesis with metyrapone is associated with decreased plasma ghrelin levels. Collectively, this suggests that stress-induced elevations in ghrelin levels may be secondary to the rise in peripheral cortisol, independent of central elevation of ACTH and possibly CRH levels.