Acylated ghrelin inhibits spontaneous luteinizing hormone pulsatility and responsiveness to naloxone but not that to gonadotropin-releasing hormone in young men: evidence for a central inhibitory action of ghrelin on the gonadal axis.
BACKGROUND
Recent evidence suggests that ghrelin exerts a negative modulation on the gonadal axis. Ghrelin was reported to suppress LH secretion in both animal and human models. Moreover, acylated ghrelin (AG) also decreases the LH responsiveness to GnRH in vitro.


OBJECTIVE
The objective of the study was to evaluate the effects of AG infusion on spontaneous and stimulated gonadotropin secretion.


METHODS
In seven young healthy male volunteers (age mean +/- sem 26.4 +/- 2.6 yr), we evaluated LH and FSH levels every 15 min during: 1) iv isotonic saline infusion; 2) iv saline followed by AG; LH and FSH response to GnRH (100 microg iv as a bolus), 3) alone and 4) during AG infusion; LH and FSH response to naloxone (0.1 mg/kg iv as a slow bolus), 5) alone and 6) during AG infusion.


RESULTS
Significant LH but not FSH pulses were recorded in all subjects under saline infusion. AG infusion inhibited LH levels [area under the curve((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 [area under the curve ((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. Because AG does not affect the LH response to GnRH, these findings indicate that the ghrelin system mediates central inhibition of the gonadal axis.
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Corso Dogliotti 14, I-10126 Torino, Italy.
Fabio
F
Lanfranco
Lorenza
L
Bonelli
Matteo
M
Baldi
Elisa
E
Me
Fabio
F
Broglio
Ezio
E
Ghigo
D000215:Acylation; D000328:Adult; D000465:Algorithms; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism; D054439:Ghrelin / Q000378:metabolism / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000009:adverse effects / Q000494:pharmacology*; D006066:Gonads / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008297:Male; D009270:Naloxone / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D011673:Pulsatile Flow / Q000187:drug effects*; D013997:Time Factors
D054439:Ghrelin; D007987:Gonadotropin-Releasing Hormone; D009270:Naloxone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone