Context: recent evidence suggests that ghrelin exerts a negative modulation on the gonadal axis. Ghrelin was reported to suppress LH secretion both in animal and human models. Moreover, acylated ghrelin (AG) also decreases the LH responsiveness to GnRH in vitro.

Objective: to evaluate the effects of AG infusion on spontaneous and stimulated gonadotropin secretion.

Design, Participants and Intervention: in 7 young healthy male volunteers (age mean±SEM: 26.4±2.6 yrs) we evaluated LH and FSH levels every 15 min during: a) i.v. isotonic saline infusion; b) i.v. saline followed by AG; LH and FSH response to GnRH (100µ g i.v. as a bolus) c) alone and d) during AG infusion; LH and FSH response to naloxone (0.1 mg/kg i.v. as a slow bolus) e) alone and f) during AG infusion.

Results: significant LH but not FSH pulses were recorded in all subjects under saline infusion. AG infusion inhibited LH levels (AUC_(240–480): 415.8±69.7 mIU/mL*min during AG vs 744.6±120.0 mIU/mL*min during saline, p<0.02), and abolished LH pulsatility. No change in FSH secretion was recorded. The LH and FSH responses to GnRH during saline were not affected by AG administration. However, AG inhibited the LH response to naloxone (AUC_(120–210): 229.9±39.3 mIU/mL*min during AG vs 401.1±44.6 mIU/mL*min during saline, p<0.01). FSH levels were not modified by naloxone alone or in combination with AG.

Conclusions: AG inhibits both spontaneous LH pulsatility and the LH response to naloxone. As AG does not affect the LH response to GnRH, these findings indicate that ghrelin system mediates central inhibition of the gonadal axis.