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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2008-0049
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The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 9 3633-3639
Copyright © 2008 by The Endocrine Society

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

Fabio Lanfranco1, Lorenza Bonelli1, Matteo Baldi, Elisa Me, Fabio Broglio and Ezio Ghigo

Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, I-10126 Turin, Italy

Address all correspondence and requests for reprints to: Ezio Ghigo, M.D., Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Corso Dogliotti 14, I-10126 Torino, Italy. E-mail: ezio.ghigo{at}unito.it.

Context: 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.

Design, Participants, and Intervention: 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 µg 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.




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C. I. Messini, K. Dafopoulos, N. Chalvatzas, P. Georgoulias, and I. E. Messinis
Effect of ghrelin on gonadotrophin secretion in women during the menstrual cycle
Hum. Reprod., April 1, 2009; 24(4): 976 - 981.
[Abstract] [Full Text] [PDF]




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Copyright © 2008 by The Endocrine Society