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Decrease in Luteinizing Hormone Pulse Frequency during a Five-Hour Peripheral Ghrelin Infusion in the Ovariectomized Rhesus Monkey

Department of Obstetrics and Gynecology (N.R.V., E.X., L.X.-Z., M.F.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; Reproductive Medicine Unit (M.G.), Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland; and The Salk Institute (J.R.), La Jolla, California 92037

Address all correspondence and requests for reprints to: Dr. Michel Ferin, Department of Obstetrics and Gynecology, College of Physicians & Surgeons, 630 West 168th Street, New York, New York 10032. E-mail: mf8{at}columbia.edu.

Ghrelin, a nutrition-related peptide secreted by the stomach, is elevated during prolonged food deprivation. Because undernutrition is often associated with a suppressed reproductive axis, we have postulated that increasing peripheral ghrelin levels will decrease the activity of the GnRH pulse generator. Adult ovariectomized rhesus monkeys (n = 6) were subjected to a 5-h iv human ghrelin (100- to 150-µg bolus followed by 100–150 µg/h) or saline infusion, preceded by a 3-h saline infusion to establish baseline pulsatile LH release. Blood samples were collected at 15-min intervals throughout the experiment. Ghrelin infusion increased plasma ghrelin levels 2.9-fold of baseline. Ghrelin significantly decreased LH pulse frequency (from 0.89 ± 0.07/h in baseline to 0.57 ± 0.10/h during ghrelin infusion; P < 0.05, mean ± SEM), whereas LH pulse frequency remained unchanged during saline treatment. LH pulse amplitude was not affected. Ghrelin also significantly stimulated both cortisol and GH release, but had no effect on leptin. We conclude that ghrelin can inhibit GnRH pulse activity and may thereby mediate the suppression of the reproductive system observed in conditions of undernutrition, such as in anorexia nervosa. Ghrelin also activates the adrenal axis, but the relevance of this to the inhibition of GnRH pulse frequency remains to be established.

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